The Expendables—leader Barney Ross, knife specialist Lee Christmas, hand-to-hand combat specialist Yin Yang, heavy-weapons specialist Hale Caesar, demolitions expert Toll Road, the unstable Gunner Jensen, and sniper Billy the Kid, the team's newest recruit and Ross' protégé—are deployed to Nepal to rescue Dr. Zhou, a hostage. They also rescue the captured mercenary Trench, Ross's rival. Yang leaves the group to escort Zhou back to China.
After returning to New Orleans, Billy tells Ross that he intends to retire at the end of the month and live with his girlfriend Sophia. Later, Ross is forced to accept a mission from CIA operative Mr. Church to retrieve an item from a downed airplane in Albania. Church sends technical expert Maggie Chan with the team. In Albania the Expendables retrieve the item, but are then ambushed by international criminal and arms dealer Jean Vilain, his right-hand man Hector and his mercenary group (the Sangs), who have captured Billy. Vilain demands the item in exchange for Billy's life. The team gives up the item, but Vilain roundhouse kicks a knife through Billy's heart and flees with the Sangs by helicopter. Ross recovers a note for Sophia from Billy's body; the team buries their fallen comrade, swearing vengeance on Vilain.
Maggie tells them that the item is a computer, with the location of five tons of refined plutonium abandoned in a mine by the Soviet Union after the Cold War. Vilain intends to retrieve the plutonium and sell it. The Expendables are able to weakly track the computer's signal and follow Vilain, which leads them to Bulgaria where they stay overnight at an abandoned Russian military base. The next morning, the team is ambushed by the Sangs and a tank. After the Expendables run out of ammunition, they are saved by Ross's old friend, Booker, who quickly eliminates both the Sangs and the tank. Before he departs, Booker informs the group of a nearby village whose residents oppose Vilain. Meanwhile, Hector and Vilain dig up the plutonium and begin collecting it.
In the village, the Expendables find several armed female villagers guarding their children from Vilain's forces. The local inhabitants are taken and put to work as slaves in the mine, never returning, and the women ask for the Expendables' help. The Sangs arrive for more villagers, but are ambushed by the Expendables and killed. After locating Vilain and the mine, the team assaults the area with their plane before deliberately crashing into the mine. The team saves the enslaved miners from execution, but Vilain and Hector escape with the plutonium. Vilain remotely detonates explosive charges in the mine; it collapses, trapping the miners and the Expendables.
Church and Trench arrive, freeing the miners and the team, and join the Expendables to pursue Vilain. The group intercepts Vilain and his men at an airport as he prepares to leave by plane. Joined again by Booker, the Expendables, Trench and Church engage the Sangs in battle. Christmas decapitates Hector, while Ross and Vilain fight hand-to-hand. Ross defeats Vilain, stabbing him and avenging Billy.
In the aftermath, Ross is given an old Antonov An-2 biplane by Church; Church, Maggie, Booker and Trench then leave the team. In France, Sophia discovers a box on her doorstep with a large sum of money and Billy's letter. As the Expendables depart in the plane, they propose a final toast to Billy.
