Arthur Leander collapses and dies on a Toronto stage performing King Lear. Jeevan Chaudhary rushes from the audience to help, meets Kirsten Raymonde backstage, then receives a phone call that changes everything: the Georgia Flu has arrived and is spreading faster than anything in medical history.

Twenty years after the collapse, Kirsten Raymonde travels with the Traveling Symphony through the Great Lakes settlements. The troupe performs Shakespeare and music. The Symphony arrives at St. Deborah by the Water to find something has gone wrong — members left behind on a previous trip have disappeared, and a man called the Prophet controls the settlement.

The novel moves into Arthur Leander's pre-collapse past: his rise from a small island in British Columbia, his first marriage to Miranda Carroll, his Hollywood success, and the gradual erosion of his ability to stay present in his own life. Miranda is introduced working on her graphic novel — 'Station Eleven.'

Jeevan and his brother Frank shelter in Frank's apartment as Toronto collapses below them. They watch the city go dark from the fourteenth floor. Frank, a paraplegic writer, refuses to leave when the food runs out. Jeevan leaves alone, the last member of his family.

Clark Thompson, Arthur's oldest friend, becomes stranded at Severn City Airport in the early days of the collapse. Twenty years later, he has built the Museum of Civilization in the terminal — a collection of objects from the old world, preserved for the people who never knew it.

Expanded view of Miranda Carroll's life — her years creating the 'Station Eleven' graphic novel, her divorce from Arthur, her subsequent career as a shipping executive, and her death in Malaysia on the first day of the Georgia Flu's spread there, alone but not unhappy.

The Prophet's identity is revealed as Tyler Leander — Arthur's son, raised by his devout mother Elizabeth through the collapse years. Tyler has built a theology of the flu as divine cleansing and commands absolute loyalty in the settlements he controls. The Symphony flees his pursuit as the narrative threads converge.

The narrative threads converge at Severn City Airport. Kirsten and the Symphony arrive at the Museum of Civilization. Clark meets Kirsten and encounters the Station Eleven comics for the first time — Miranda's work, unknowingly preserved. The novel ends with a glimpse of lights visible from the airport — electricity, beginning again somewhere to the north.