The following version of this book was used to create the guide: El-Mohtar, Amal; Gladstone, Max. This Is How You Lose the Time War. Saga Press, 2019.

The novel is divided into 25 chapters, and nearly all of them conclude with letters written between Red and Blue, the two main characters. Red and Blue are futuristic beings that work on opposing sides as soldiers in a time war. Red works for the Agency, whose interests seem to lie in bolstering technology through the years and ensuring society advances; Blue works for the Garden, whose aims are opposite in that they often hope to take down technologies, like steamships, in order to stop the future rise of certain technologies.

The novel starts with Red, who is looking for Blue in order to eliminate her so she cannot thwart the Agency's plans. They exchange letters taunting one another for not being able to reach the other. The two go around on missions. Red eventually sends Blue a letter as she tries to disable the growing steam industry, and she says that people from the Agency do not need to eat and can shapeshift.

Red watches Atlantis sink and receives a letter from Blue talking about the concept of hunger and whether she can even feel it. Red talks about a time when she went to a hilltop to think like Socrates did, which alienates her from the other Agency members, who tend not to do things like that. They begin to bond over what separates them from their peers. Blue writes to Red, saying she longs for serious friendships and relationships with beings who are like her.

Red and Blue end up in the same strand, and Blue runs away when she sees Red. However, she sees an animal that looks threatening to Red and brutally kills it, saving her. She leaves the strand with a letter from Red, cautioning her to keep enough distance so that the Agency and Garden do not find out about their relationship. Red starts working harder to throw her boss, the Commandant, off the scent. The two continue exchanging letters, finding more comfort and love in each other, but Red fears something may be following and watching her. Red eats sumac seeds that Blue has seeded with letters; the two continue to long to be close. She eats three of the six, but wants to kill whatever is following her before she reads the rest.

Red waits in a specific strand of time for the being following her, which she calls a shadow; eventually, it appears, but slips away before Red can kill it. Red grows impatient and eats the rest of the seeds with notes in them anyway. Blue describes how people are formed and planted in the Garden, and talks about how she was cast out for a year when she was young out of fear that she had been compromised by enemy agents, which turned out to be a false alarm. However, during that exile, she became different from other Garden members. Red voices her love for Blue in another letter.

Red is summoned to a field office by the Commandant, who exists as a mind that can inhabit various bodies. The Commandant asks Red if she knows Blue; she noticed the two had frequently been seen close together, and fears Blue is trying to groom Red to make her weak. She seems not to know the two are already in contact. She tasks Red with killing her.

Blue is contacted by a manifestation of the Garden, who fears that she is in danger and wants to remove her from the war, but Blue convinces it to keep her where she is. Red writes, scared because the Agency knows who Blue is and intends to kill her. She says she will write Blue a poisoned letter and Blue is not to read it in order to survive. She embeds the poison in seeds.

Blue eats the poisoned berries against Red's will because she fears not eating them would make the Agency suspicious of Red. Red comes to the strand where Blue ate the berries, even though this is dangerous. She grabs a letter from Blue's body and then reads it at a strand toward the world's end. She jumps off a cliff, intending to kill herself, but she slips away at the last moment.

Red, depressed, spends time underground in London, but sees a boy die in a window there who looks a lot like Blue, which she takes as a sign that Blue is still somewhere out there, not dead after all. Red breaks the tracking systems inside her and goes to each of the places she received letters from Blue looking for clues. The Agency at this point has deemed her treasonous, picking up on her intentions, and is hunting her. Red crashes into the Garden after traveling backwards through time and fights the hostile atmosphere looking for a young Blue. She finds her as a young being and gives her a small taste of the poison she will use in the seeds in the future, hoping to steel her body against it and save her from death. This poison is implied to be what forced the Garden to exile her for a year, as explained earlier on. The Commandant captures Red after she leaves.

Red is imprisoned, and the Agency interrogates her as to what her intentions were in entering the Garden. A guard asks her why she did not just join the Garden when she had the chance, and Red hears a hint of Blue's voice in the guard's. She finds a letter on the floor of her cell from Blue, who is still alive, not having died from the poison after all. She leaves Red instructions on how to escape so that the two can live together, even though they will be hunted fiercely.