In a flashforward, we meet a battered Lori Loud waking up to her hometown, Royal Woods, in ruins. She enters her house and kills the "roamer" inside. She then sits next to the dead roamer and laments over the events that occurred in the past years.
We are now in the present, first following an ill Lynn Loud in her house. She is the first to find out about the roamers when she sees a roamer attack live on television. We then switch to Lincoln Loud and Clyde McBride, who are walking around school. There they hear about a rumor that roamers are in Royal Woods. We then switch over the protagonist of the story, Lori. She is talking with her friends before Leni Loud asks Lori to accompany her in the bathroom. Lori goes with Leni and does her makeup as the two talk. They share a peaceful moment of sibling bond, for what may be the last time as they come out of the bathroom to a school under attack by cannibalistic people. They find Luan Loud and escape, though they worry about Luna Loud. Luna, as it turns out, overslept and is now taking a bus to school. However, the bus breaks down and the bus driver is attacked by a roamer. In the chaos, Luna grabs a crowbar and escapes.
Lori drives to the elementary school and attempts to find the rest of her siblings. They warn the staff and the students of roamers, which quickly sends the school into a panic. They find their siblings, as well as Ronnie Anne and Bobby Santiago, the both having arrived earlier by plane. All of them escape the school and make their way home.
On the way home, Lori and her siblings come across their parents and Lily, as well as Clyde's parents. They take shelter in the Loud house, surrounded with nothing but fear. When they learn about a safezone in Detroit, they get ready to head there. But first, the Louds take on the roamers outside of their house using makeshift weapons they had lying around their house. After taking out the roamers, they leave the house and head to Vanzilla, their vehicle of choice.
On the way to Detroit, Lynn Sr. takes a pit stop and gets some gasoline to refuel Vanzilla. He has a heartfelt conversation with Bobby and has him promise that he will always be there to protect Lori. Bobby promises. The two head back to the van and head for Detroit.
The Louds and the McBrides arrive in Detroit, and are checked by soldiers from the U.S. Army. They are then allowed to enter the safezone and are assigned a room in one of the buildings. While getting lunch, they encounter Sergei, Lynn Sr.'s boss, who's making their food.
They get comfortable in their seats in a cafeteria. There, Luna finds Sam alive and well, though the same could not be said for her family. Likewise, Luan finds Benny alive and well, along with his father. After finishing their breakfast, Lori, Bobby, Lincoln, Clyde, Ronnie Anne, and Lynn leave the building and go look for their other friends. Lincoln and Clyde find Liam, Rusty, Zach, and Rocky. Lori finds Chaz. It is here in this building where General Black introduces himself to the crowd in the cafeteria. He tells the residents that they could go to him if they have any questions or concerns. He then leaves, and moments later, Lori and the others leave too.
In another building, Lori and the others find Chunk, who immediately heads for Building A where the rest of the Louds are. He reunites with Luna and Sam while Lori and the others go to Building D, the last building of the Safe-Zone. There, Lynn finds Francisco, Lincoln finds Tabby, and Lori finds Carol, who she hates.
After returning back to their room, the Louds and the McBrides fall asleep peacefully, something that will soon become a rarity.
When the group wakes up, they come to Lisa for questions about the infected. Lisa states that all she knows is that a bite is enough to kill a person and transform them into one of the roamers. The only way to kill a roamer is to destroy their brain. Lisa also theorizes that Lynn is infected with the same virus that turns people into roamers, but she has managed to survive it. However, it is possible that if Lynn dies, she will turn into a roamer, even if she is not bit.
The group have breakfast together and Luna introduces her family to Sam. Rita reveals that she knows Luna likes Sam and reassures her that she and Lynn Sr. don't judge her at all. The group seems to be at peace again.
Chaz flirts with Chaz, Lucy talks with Rocky, and Tabby hangs out with Lincoln's friends. Lincoln's sense of security is shaken by Zach's suspicion that the soldiers in the Safe-Zone have a sinister motive. Although the others think he's crazy, Lincoln believes Zach may have a point.
In the meantime, General Black warms up to Rita and Lynn Sr. He gives them the baby crib that they requested.
Later, a strange man in a suicide vest threatens the soldiers in the Safe-Zone before getting caught and detained. While locked in a basement, he attempts to set off the explosives in his vest, but is stopped before he could do so. General Black and his lieutenant, Lt. Lead, interrogate the man for information about other collaborators. The man gives up Tim Crowley, a longtime nemesis of Black. Meanwhile, the soldiers outside the Safe-Zone report shooting an escapee that resembles Tim. Black checks for himself and confirms that it is Tim Crowley that they killed. He gloats at the fact that he finally killed him. Now, no one stands in the way of implementing Project Exodus.
Black lets the residents of the Safe-Zone know that he weeded out terrorists. Now feeling that the place is safer, Howard and Harold McBride seek volunteer work. They head to Black's office where Black's intense bigotry and psychopathic tendencies lead him to murder Howard and Harold. He keeps their bodies in the basement of his office.
At midnight, Lynn and Lana use a fire escape to sneak outside of Building A. They think nothing of it and tell Lincoln about it. However, Lincoln tells them to sneak out.
Later, Clyde panics about not having seen his parents yesterday night and now. Noticing this, Private Lukeman tells General Black. Black covers up the murder by telling the residents of the Safe-Zone that Harold and Howard are working. Black wants to give out jobs for all the adults, so he proposes for them to meet outside in the center of the Safe-Zone later that day.
Suspecting foul play, Lincoln, Lynn, and Lana sneak into Black's office and break into his basement. With Lana on the lookout, Lincoln and Lynn find the corpses of Howard and Harold. Lynn takes the USB from the "terrorist's" corpse and leaves the office in a state of rage. She plugs the USB into one of the office computers, though the downloading speed is abysmal.
While waiting, Lynn paces around, which Rita takes a sign of boredom. She tries to get the family together to play games, but Lincoln and Lynn are too traumatized to partake in it. That night, Lynn Sr. and Rita head to the ground floor while the USB finishes downloading a video. In the video, which all the Loud siblings watch, reveals the "terrorist" to be Gerald Brooker, a former NSA agent, who warns the viewers about General Black. He also reveals that Black is a part of a larger organization known as K.H.A.N. whose forces are situated in numerous places across the country.
The Louds attempt to warn their parents, but alarms go off and the soldiers force every minor to head into a bunker. After all the minors are accounted for, the soldiers begin to fire at the adults outside of the bunker, massacring many of them. The survivors, which include Lynn Sr., Rita, and Sergei, are taken into helicopters where they will be experimented on in a different location.
The soldiers evacuate and after leaving, the helicopters drop napalm on the Safe-Zone, essentially destroying it. Trapped inside the bunker, the Louds are left wondering about their fate...
