Six weeks into the Delphic Expanse, Captain Archer and his crew are still searching for clues regarding the mysterious Xindi. They're also adjusting to the newest members of the crew, a squad of Military Assault Command Operation soldiers (MACOs), led by Major Hayes. The crew learns of a Xindi working at a mining complex, and set out to track him down. Once they reach the complex, Archer and Reed head down to the grimy mine and meet with the alien Foreman. The Foreman offers a severed finger that he claims belongs to the Xindi worker. In exchange for a meeting with the worker, the Foreman demands a half liter of liquefied platinum. Back onboard, Phlox analyzes the finger and confirms that it is from a Xindi - however, it bears some intriguing variations from the Xindi inactive person that was recovered on Earth. The inactive person, Phlox explains, was reptilian. The finger is not.

As Enterprise ventures deep into the Expanse, the ship is rocked by inexplicable, destructive spatial anomalies that distort the laws of physics. The anomalies take most of the ship's primary systems off-line, leaving Enterprise without weapons or warp capabilities.

In scanning the Xindi database obtained from the marauder ship, Captain Archer manages to discern that the Xindi recently visited a nearby planet, and plans to see if it will provide any more clues regarding the mysterious species.

As Enterprise ventures deeper into the Expanse, the Xindi council continues to monitor its mission. The various members of the council also continue to disagree on the best course of action. The Xindi-Reptilians and Xindi-Insectoids are ready to take action against the humans, but Degra, the Xindi-Humanoid who is building the mysterious weapon, advises caution. The other Xindi species ultimately support Degra, agreeing that he needs more time to complete this weapon and that they shall proceed as planned.

Enterprise picks up a distress call from a Vulcan ship, the Seleya, which T'Pol recognizes as a ship she once served on. The ship is located in a somewhat treacherous asteroid field - the asteroids are moving in a chaotic, unpredictable pattern due to the Expanse's spatial anomalies. Archer, Reed, T'Pol and Corporal Hawkins set out for the ship in a shuttlepod and are encouraged when there appear to be bio-signs onboard. Once they board the Seleya, however, it appears eerily deserted. Apparently, the Vulcans were attempting to line the ship with trellium, but didn't get very far. As the team continues to explore the ship, they are surprised by several hugging, zombie-like Vulcans who attack them. The crew manages to fend them off, but the strangely altered Vulcans block them from the airlock, cutting off their escape route to the shuttlepod. What's worse, T'Pol seems to be suffering from the same symptoms as the crew of the Seleya.

Hoshi is in her quarters one night when she hears whispering and spies a mysterious figure lurking in the shadows. She alerts Reed, but when she turns back to the figure, it has disappeared. Reed scans for intruders, but nothing turns up. Later, as Hoshi attempts to translate some of the Xindi database, she once again hears voices and sees the mysterious figure. She also has a vision of being in a strange alien sanctuary. Alarmed, Hoshi visits Phlox, who examines her but doesn't find anything out of the ordinary. As they talk, the mysterious alien presence once again visits Hoshi - in the form of Phlox. He tells her that he's been studying her mind for several days and that he has a form of telepathy that only works in rare instances. He also tells her that he knows Enterprise is on an urgent mission and would like to talk to her about it.

On a tip from Hoshi's telepathic admirer, Tarquin, Archer and the crew head to a nearby planet, hoping to learn more about the mysterious Xindi weapon. Archer, Reed and Major Hayes embark on a reconnaissance mission and discover that the sparsely-populated planet is home to an elaborate Xindi-Sloth manufacturing plant producing canisters of a substance called kemocite. The team manages to swipe one of the canisters, which is then transported onboard Enterprise for analysis. Unbeknownst to the Enterprise crew, Degra, one of the Xindi-Humanoids, is close to testing the weapon and needs only one more shipment of kemocite to do so.

Twelve years in the future, Archer finds himself living in a modest home on a desolate planet with T'Pol as his caregiver. The last thing he remembers is walking down a corridor on his way to the Bridge. T'Pol explains that an anomaly hit the ship, and Archer knocked her out of the way of a distortion wave just in time. The wave rendered him unconscious, and when he awoke, Phlox had troubling news: Archer was infected with several clusters of parasites, which prevented him from forming long-term memories. Over the next few months, Phlox searched for a cure, but was unsuccessful - the organisms are from a domain outside of normal space-time, and none of his treatments had any effect. Meanwhile, T'Pol was granted a field commission and promoted to captain. After several months of searching, the crew learned where the Xindi weapon was being constructed - but the Xindi caught wind of it and sent ships to intercept Enterprise. The ensuing battle left Enterprise heavily damaged, and though the crew eventually located the facility where the weapon was being constructed, it had already been launched. Earth was destroyed. T'Pol relates to Archer that the Xindi also managed to destroy every human outpost they could find - only 6,000 humans are left.

The crew of the Enterprise discovers about 6,000 humans on a Delphic Expanse planet living in settlements that are similar to those of the Old West. Archer, T'Pol and Trip disguise themselves and head down to observe, hoping to learn how these settlements came to be. Reporting from Enterprise, Reed notes that scans indicate that there's also a nearby settlement of aliens.

During a test on the warp engine, Trip is seriously injured and falls into a coma. His heroic actions do save the ship from a breach, but Enterprise sustains damage and is left drifting in a dangerous polaric field. Phlox is concerned that Trip may not survive, and poses one potentially controversial alternative: using one of his creatures, a Lyssarrian Desert Larvae, Phlox could clone Trip with a simbiot, then use its neural tissue for a transplant. The simbiot would have Trip's genetic make-up, but it would grow old and die in a span of 15 days. Archer is uneasy about this plan, but he eventually decides that he has no choice: he must complete his mission and he needs Trip to do so.

Archer receives a surprise visit from Daniels, the mysterious time traveling operative who has aided him in the past. Daniels tells Archer that three Xindi-Reptilians have somehow traveled back in time 150 years to Detroit, Michigan. He wants to send Archer and T'Pol back in time to investigate. He also gives Archer temporal tags to bring back anything that doesn't belong in the 21st century. After disguising them in clothing from the proper time period, Archer and T'Pol successfully travel 150 years in the past, arriving at night on a Detroit City street.

After coming to the aid of a crippled alien vessel, Captain Archer brings the ship's crew onboard Enterprise for medical attention. The aliens are a deeply religious people known as the Triannons, and Archer invites their leader, D'Jamat, to dinner. D'Jamat explains that the Triannons regard the Delphic Expanse as the "Chosen Realm" and the mysterious spheres are sacred objects created by god-like beings known as the "Makers". The spatial anomalies, D'Jamat says, are merely "the Makers' breath".

When Hoshi identifies a signal that matches the kemocite Archer planted on a Xindi ship, the captain realizes that this could lead Enterprise closer to the Xindi weapon. He orders T'Pol to set a course. The course, however, requires Enterprise to navigate a dense field of spatial anomalies and the ship sustains heavy damage. Just as it looks like Enterprise may not emerge intact, the ship is hauled out by an Andorian vessel helmed by Commander Shran, who has had dealings with Archer in the past. Shran offers assistance to Enterprise, claiming that the Andorians wish to help the humans in their quest for the Xindi. Though T'Pol is suspicious of the Andorians' motives, Archer accepts. Shran sends his tactical officer, Lieutenant Talas, to assist Reed in repairing Enterprise's weapons. Like T'Pol, Reed is skeptical of the Andorians, but he soon finds himself bonding with Talas - the two have similar backgrounds.

Upon returning to the Xindi weapon test site, the crew of Enterprise detects a Xindi ship in the area. They attack and board the ship, taking its occupants prisoner. Among the prisoners is Degra, the Xindi-Humanoid who is also the mastermind behind the superweapon. Unfortunately, the Xindi ship's databanks have been mostly erased and Degra and his men are less than helpful. Phlox, however, has discovered an interesting wrinkle in Xindi neurophysiology - it's possible to erase their most recent memories. Archer formulates a plan that involves Phlox erasing Degra's memories and Trip building a small mock shuttlecraft that will be housed on Enterprise.

As Enterprise heads for the red giant star that Archer believes to be the location of the Xindi weapon, the ship encounters a massive spatial distortion. They discover a small craft within the anomaly and pull it to safety. Inside the craft, they find an unconscious alien being hooked up to monitoring equipment. The alien, notes Phlox, is suffering from rapid cellular degeneration. Once revived, the alien insists on being returned to his ship, but Archer can't help but be suspicious of his motives.

En route to Azati Prime, Archer and his crew encounter another roadblock: a trans-dimensional disturbance. To pass through it could prove deadly for the crew, but going around it means another two-week delay. Luckily, Phlox has a solution. He will place each crewmember in a comatose state, so as to protect their neocortexes while they traverse the anomaly. Because Phlox's Denobulan physiology is immune to the effects of the disturbance, he plans to remain conscious and watch over the ship and crew. As there's no way of knowing what effects the disturbance will have on Enterprise's warp drive, Trip recommends leaving the ship at impulse, meaning Phlox will have to keep the crew sedated for at least four days. Phlox is briefed on how to perform various tasks in case of an emergency - Mayweather gives him a quick helm tutorial while Trip instructs him on checking the warp engines. Various crewmembers express their concern about Phlox running the ship, because he lacks Starfleet training, but Archer is confident the doctor can handle things.

On the way to Azati Prime, Enterprise discovers a damaged Xindi-Insectoid vessel with no bio-signs onboard. Archer, Reed, Trip, T'Pol and Major Hayes board the vessel, hoping to learn more. They discover a pair of Insectoid inactive persons, a small assault vehicle and an eerie hatchery containing Xindi eggs, some of which are still viable. As the team explores the ship, Archer is suddenly spattered by a strange liquid that spews from one of the egg sacs.

Enterprise has finally reached Azati Prime, the site of the Xindi superweapon. Unfortunately, Reed can't find any weak spots in the Xindi's formidable detection grid. Archer suggests utilizing the Insectoid shuttle the crew recently salvaged to sneak past the grid and locate the weapon - perhaps they will be able to blend in. After learning how to operate the craft, Mayweather and Trip take it into Xindi territory, hoping to scan the weapon. They clear the detection grid and find that the planet is largely oceanic. They detect what could be the weapon, so they take the shuttle underwater. Once there, they find what they're looking for: the weapon is massive, a truly impressive and horrific sight. They take their scans and head back to the ship. Meanwhile, Enterprise is detected and scanned by a Xindi monitoring facility on the moon's surface. Archer, worried that the facility will alert the rest of the Xindi, is forced to destroy it.

As Enterprise continues to endure the brutal Xindi attack, the crew struggles to hold the ship together. Suddenly, the Xindi ships cease firing and begin to move off. The crew is relieved, but Enterprise has sustained heavy damage and will require extensive repairs before the mission can continue. Meanwhile, Archer has been released from his imprisonment by the Xindi-Reptilians and is returned to Enterprise in a Xindi-Aquatic escape pod. Archer isn't sure why the Xindi returned him to his vessel, but he believes he may have gotten through to Degra. As Archer briefs T'Pol on his ordeal, he can't help but notice that she's acting somewhat strangely - her emotions seem close to the surface and her hands appear to be shaking uncontrollably. There's no time to dwell on this, however - Enterprise still requires a lot of work in order to be fully operational.

Enterprise is still undergoing repairs, but Captain Archer is determined to make it to Degra's rendezvous point on time. The crew, however, is still reeling from the loss of the 18 crewmen who died during the Xindi attack. The loss seems to be hitting Trip especially hard, particularly when Archer orders him to write a letter of condolence to an engineering crewman's family. T'Pol, meanwhile, is dealing with problems of her own - she's coping with the lingering effects of her trellium addiction, and is finding her emotions difficult to control. Phlox points out that the addiction caused serious damage to her neural pathways. She may have to learn to live with these emotions.

As Enterprise heads toward its rendezvous with Degra and a fateful meeting with the Xindi Council, the crew faces a dangerous trek. To reach their destination, they must enter a subspace corridor guarded by the Kovaalans, a species that isn't very tolerant of trespassers. As Archer attempts to devise a game plan, the crew detects another ship. Strangely enough, it's an NX-class Starfleet vessel ... and as it approaches, it becomes apparent that its designation is Enterprise NX-01!

With Degra's help, Captain Archer prepares to meet with the Xindi Council. As they go over their plan, Degra offers a little background on the Sphere-Builders' involvement with the Xindi. After the Xindi homeworld was destroyed, the Sphere-Builders began appearing to the survivors, guiding them to habitable planets and valuable resources. Because of this, the Sphere-Builders are worshipped by the Xindi and are referred to as "the Guardians". This belief, Degra explains, is what Archer's up against.

The Xindi-Reptilians have kidnapped Hoshi, hoping that she will be able to decipher the Aquatics' launch code. This will give them the three codes they need to deploy the superweapon and destroy Earth. Hoshi refuses to cooperate, so Commander Dolim has her injected with parasites that invade her neocortex and render her more compliant.

Aboard Degra's ship, Archer, Reed and Hoshi work with the Arboreals and Primates to stop the Xindi weapon from launching. Archer plans to destroy the weapon from the inside by overloading the power systems, but he needs Hoshi to decrypt the weapon schematics. A ragged Hoshi is still recovering from her ordeal with the Reptilians, but she's determined to help. Despite her condition, Archer plans to take her with him when he boards the weapon. As Archer outlines his plan, he suddenly finds himself transported to a futuristic council hall - he's face-to-face with Daniels, the mysterious time-traveling operative he's encountered many times before. Daniels tells Archer that he's going to be a crucial part of forming the "United Federation of Planets" that Daniels has spoken of before. He urges Archer not to go on this mission and to send Reed or someone else. Others are not crucial to the future of mankind - Archer is. Archer, however, won't be swayed. He's determined to complete the mission himself.