Amanda Waller decides to assemble the Suicide Squad on behalf of the United States government. Harley Quinn is arrested after Batman intervenes on a business deal between the Joker and a weapons dealer, Monster T, and ends up being recruited into the Suicide Squad alongside Deadshot, Boomerang, Killer Croc, El Diablo and Slipknot. Rick Flagg is assigned to lead them with Katana as his second-in-command.
Meanwhile, June Moon is possessed by the Enchantress and decides to revive her brother, the Incubus, and retrieve her heart, which is in Waller's possession. She attacks Midway City, filling it with monsters, and uses Monster T to host the Incubus. The Suicide Squad is sent to kill her, but end up being shot down by the Joker and his men, who want Harley back.
After they're shot down, Slipknot tries to escape and is killed by a bomb implanted on his neck. The team transverses the city fighting monsters, and ultimately fights the Incubus in a subway station, while the Enchantress captures Waller. Diablo sacrifices himself to destroy the Incubus, and the team goes to rescue Waller. They fight the Enchantress in an abandoned museum and Harley destroys the heart, exorcising the Enchantress.
Waller still locks everyone up, but the Joker later breaks into the prison and rescues her. Movie ends with them locking eyes and smiling.