The team, tired of being stuck in Doom Manor, decides to visit the local town while The Chief is away. However, this seemingly harmless field trip leads to some grave consequences, including an encounter with the mysterious and powerful Mr. Nobody.

Following Mr. Nobody’s capture of Niles Caulder and the destruction of Cloverton, Ohio, The Doom Patrol investigate the mysterious albino donkey and discover it is a door to another universe, one where Mr. Nobody is in control. Cyborg aka Vic Stone, a part man/part machine hero from Detroit who has his own complicated relationship with Niles Caulder, joins the search.

Following the only lead in the search for Niles Caulder, the Doom Patrol sets out for Paraguay and discovers Dr. Von Fuchs, the Nazi doctor who transformed Eric Morden into Mr. Nobody, and learns the connection between Niles and the two villains.

As the team recovers from the fight at Fuchtopia, Willoughby Kipling, an old friend of Niles', unexpectedly conscripts the Doom Patrol into helping him avert the end of the world by stopping a cult, but the team fails and the apocalypse begins.

With the Apocalypse in full swing, the Doom Patrol must work with an unlikely ally and a very special pug to stop the end of the world.

Following a clue left by Mr. Nobody, Jane, Larry and Rita visit a school where Niles' previous team of heroes, the original Doom Patrol has retired; Cliff and Vic tenuously bond over their mutual "father issues."

After a violent outburst from Cliff, the team engages in some self-led group therapy, leading to some growth within the group as they are knit closer together.

Danny, a sentient, gender-queer, teleporting street who is being hunted by secret government agency the Bureau of Normalcy, needs help from Niles but he gets Vic and Larry instead. Cliff and Rita track down Karen, one of Jane's personalities.

Jane retreats into The Underground, a treacherous place deep within her own mindspace, where she encounters her many personas and dark traumas of her past.

Vic and Rita find the mansion infiltrated by Ernest Franklin, a dangerous man called the Beard Hunter, who has been activated by the Bureau of Normalcy to find Niles Caulder, the tragic love story that started Niles on the path toward the man he is.

While Larry pays a visit to his lost love, John, both in real life and in the Dreamscape. Cliff travels with Rita down to Gator Country to reconnect with his daughter after 30 years; Jane and Vic pursue the "Hero of the Beach."

With Vic captured by the Bureau of Normalcy and held at the Ant Farm, his father, Silas Stone, hatches a plan to break him out with the rest of the Doom Patrol, but everything doesn't go according to plan.

After escaping the Ant Farm with Flex Mentallo, the Doom Patrol tries to restore his memory and abilities in order to find the Chief; Rita confronts her doubts with the help of a stranger, and Larry realizes how tied he is to the Negative Spirit.

The Doom Patrol finally lands on the threshold of rescuing the Chief from the clutches of Mr. Nobody. With help from Flex Mentallo and Danny the Street, the group enters the White Space, where Mr. Nobody offers a chance to start again.

In the wake of the Chief's revelation, the members of the Doom Patrol go their separate ways. When Mr. Nobody hatches a new plan, the team must reunite to help the Chief with a new, unexpected and weird threat to the world.