Physicists Abby Yates (Melissa McCarthy) and Erin Gilbert (Kristen Wiig) are co-authors of a research book which posits the existence of paranormal phenomena such as ghosts. Erin has disowned the work and become a professor at Columbia University, while Abby continues to study the paranormal at a technical college with eccentric engineer Jillian Holtzmann (Kate McKinnon). Erin learns Abby has republished the book, threatening her bid for tenure at Columbia. She reunites with Abby and, in exchange for Abby removing the book from publication, reluctantly agrees to assist her and Jillian in a paranormal investigation.
The group witness a malevolent ghost (Bess Rous), renewing Erin’s belief in the paranormal. However, a video of their investigation is posted online, and Erin is fired by the university. She joins Abby and Jillian’s project, but when a new institute director learns its nature, he fires them. They open an office above a Chinese restaurant and call themselves the “Conductors of the Metaphysical Examination.” They build equipment to study and capture ghosts, and hire dimwitted but handsome Kevin Beckman (Chris Hemsworth) as a receptionist.
MTA worker Patty Tolan (Leslie Jones) witnesses a ghost in a subway line and contacts the group. They document the ghost and successfully test Jillian’s proton containment laser, but their findings are again dismissed. They continue to develop their technology and advertise their services as what pundits have dubbed the “Ghostbusters”. Patty joins the team, providing historical knowledge of New York City and a repurposed hearse, “Ecto-1”.
Unbeknownst to them, the ghosts are being summoned by devices built by Rowan North (Neil Casey), an occultist and mad scientist attempting to bring about the “apocalypse”. When Rowan plants another device at a live music venue, the Ghostbusters are called in and capture the ghost in front of the audience. When supernatural debunker Dr. Martin Heiss (Bill Murray) challenges the Ghostbusters, the incensed Erin releases the ghost as proof; it throws Heiss out a window, presumably to his death, before escaping. The Ghostbusters are brought to see Mayor Bradley (Andy García) and his loyal secretary, Jennifer Lynch (Cecily Strong), who reveals that the city and the Department of Homeland Security are aware of New York’s ghost problem. While privately supporting the team’s work, the mayor’s office and DHS publicly denounce them as fraudsters.