It's early 1945 and General MacArthur has returned to the Philippines to battle the Japanese forces and retake the country. Yet, in the path of the massive Allied forces are Japanese POW camps filled with survivors of the notorious Bataan Death March from three years earlier. The U.S. military doesn't want them to be collateral damage from the advance, and they're aware that the new Japanese edict is that all POWs be killed.
Accordingly, Lt. Colonel Henry Mucci (BENJAMIN BRATT) of the 6th Army is assigned to stage a rescue of 500 some men from the Cabanatuan POW camp that's located some thirty miles behind enemy lines. Mucci chooses Captain Bob Prince (JAMES FRANCO) to conceive and execute the raid, and their outnumbered but determined forces then set out for the camp, eventually joined by Filipino guerillas led by Capt. Juan Pajota (CESAR MONTANO).
Back at the camp, things briefly look up for POW leader Major Daniel Gibson (JOSEPH FIENNES) and others, such as Captain Redding (MARTON CSOKAS), when the Japanese guards suddenly leave them there alone. Gibson is sick with malaria, but thanks to supplies smuggled in from Manila by his friend and lost love Margaret Utinsky (CONNIE NIELSEN) and her local assistant Mina (NATALIE MENDOZA), he's been able to keep the illness at bay. Yet, crackdowns on such smuggling are increasing each day, led by secret policeman Yamada (GOTARO TSUNASHIMA).
Things get worse when a new contingent of Japanese soldiers and guards arrive to run the camp, led by the stern Major Nagai (MOTOKI KOBAYASHI) who informs the prisoners that for every one who escapes, ten will die in his place. As he awaits word to execute all of them, the POWs try to hold on, all while Mucci, Prince and their forces slowly make their way toward the camp for their upcoming rescue raid.