Authors Erin Gilbert (Kristen Wiig) and Abby Yates (Melissa McCarthy) write a book in which they claim that ghosts exist. A few years later, Erin lands a prestigious teaching position at Columbia University, but when her book resurfaces, she becomes a joke within the academic world.

That changes when ghosts invade Manhattan, and Erin and Abby reunite in order to get together a team to save the world.