John "Hannibal" Smith (Liam Neeson) is held captive in Mexico by two Federal Police officers working for renegade General Javier Tuco. Hannibal escapes and sets out to rescue Templeton "Faceman" Peck (Bradley Cooper), who is held captive at Tuco's ranch. Hannibal saves Face after enlisting fellow Ranger BA Baracus (Quinton Jackson), driving to the rescue in BA's modified GMC Vandura van. Pursued by Tuco, they stop at a nearby Army Hospital to recruit the services of eccentric pilot Howling Mad Murdock (Sharlto Copley). They flee in a medical helicopter, chased by Tuco, in a dogfight that leaves BA with a fear of flying. The battle ends when they lure Tuco's helicopter into American airspace, where it is shot down.
Eight years later in Iraq, Hannibal is contacted by CIA Special Activities Division operative Lynch (Patrick Wilson), who assigns them a black ops mission to recover U.S. Treasury plates and over $1 billion in cash from Iraqi insurgents slated to move it out of Baghdad in an armored convoy. Hannibal's commanding officer, General Morrison (Gerald McRaney), consents to the operation but Face's former lover, DCIS Capt. Charissa Sosa (Jessica Biel), tries to discourage the team against getting the plates. The mission is successful; when the team returns to base, however, the money and Morrison's vehicle are destroyed by Brock Pike (Brian Bloom) and his men from the private security firm Black Forest. Without Morrison (the only proof that they were authorized to act), Hannibal, Face, Murdock, and BA are court martialed where they are sentenced to ten years in prison and dishonorably discharged. Sosa also ended up court martialed and is demoted to lieutenant.
Six months later, Lynch visits Hannibal in prison and tells him that Pike may be trying to sell the plates with the help of an Arab backer. Hannibal, who has been tracking Pike on his own, makes a deal with Lynch: full reinstatement and clean records for his team in return for the plates. Lynch agrees and Hannibal escapes, breaking out Face, BA, and Murdock in the process. Sosa is hot on the team's trail. The team hijacks a military Lockheed C-130 Hercules aircraft, which is later shot down by Reaper UCAVs, but not before the team flies away in a tank stashed aboard and make it to the ground safely. The team moves to reclaim the plates and kidnap Pike's backer. It is revealed that the backer is actually General Morrison, who plotted with Lynch and Pike to steal the plates but teamed up with Pike to double-cross Lynch and fake his death. Lynch orders an airstrike to kill the team and Morrison, but the team manages to escape.
Hannibal arranges to meet Sosa on board a container ship at the Los Angeles docks, saying he will hand over Morrison and the plates. Face then calls Sosa on a drop phone he planted on her at the train station, and conspires a different plan with her. It all unfolds according to plan until Pike, who is now working with Lynch, blows up the container ship and chases Face to near death. BA finally gives up his pacifist ways and kills Pike, saving Face. Hannibal leads Lynch into a container with Murdock, who, wearing a covered bullet-proof helmet, is portraying Morrison. Lynch shoots at Murdock’s head, believing that he is killing Morrison, and is later tricked into admitting that he stole the plates, and is subsequently arrested by Sosa.
The CIA agents led by a man named "Lynch" (Jon Hamm) comes and claims custody of the other Lynch. Despite their success, the military still arrests the team for escaping from prison. Sosa is reinstated to captain, but she promises to do all she can to set the team free and kisses Face as everybody is led into a prison van. In the van, Face opens his mouth and reveals a handcuff key, given to him by Sosa through the kiss. The final scene includes a narration (spoken by Corey Burton) that is similar to the show's opening narration.