The Joker and Harley Quinn, his beloved partner in crime, are racing through Gotham's streets with sacks of stolen cash, pursued by the police. Though the Joker manages to get away, Harley is ultimately captured by a mysterious woman wielding a katana.
Meanwhile, Amanda Waller, the head of the government security organization A.R.G.U.S., has assembled a team of supervillains for a ruthless mission in another world. After losing contact with the first suicide squad sent through a portal, Waller dispatches Deadshot, Peacemaker, Clayface, King Shark, and Harley as replacements. However, shortly after entering the portal, their helicopter crashes into the middle of a battle between horse-mounted soldiers and vicious orcs.
With all the accompanying A.R.G.U.S. members killed on impact, the villains break free from their restraints and tear through the orc army, inadvertently aiding the human troops—only to be imprisoned as a reward. Now bound by magic-infused shackles, Harley and her team must hurry back to the portal they came from, or the bombs implanted in their necks by A.R.G.U.S. will detonate.