Several weeks after the attack on Pearl Harbor, Lt. Col. Jimmy Doolittle (Spencer Tracy) is ordered to assemble a volunteer force of bombers for a top secret mission.
One of the two dozen bomber crews who volunteer for the mission is led by Lt. Ted Lawson (Van Johnson), who just recently returned from his honeymoon. For about a month, the bomber crews are trained to take off in their B-25s in under 500 feet (to simulate taking off from an aircraft carrier), and to bomb targets without their usual bomb sites.
One morning, the teams are told they are to ship out immediately for California. Lawson barely has time to say goodbye to his wife Ellen before he and his crew take off. Once in California, their planes are loaded onto the USS Hornet and everyone goes on board for their trip out on the Pacific. When the Hornet is safely out to sea, the crews are finally told their mission. They are going to retaliate for the attack on Pearl Harbor by bombing Tokyo and other key military targets in other Japanese cities. After their bombing run, they are to land at a base in China. However, their ship has been spotted by the Japanese and they will have to take off earlier than expected.
The bombing run, led by Doolittle himself, is a success, and several Japanese targets are destroyed. But because the planes were forced to take off further away from their targets than was originally planned, all of the planes run out of fuel before they can reach the Chinese base. Lawson and his crew are forced to crash-land on a beach near a remote fishing village in Japanese-held territory in China. All of the men are injured, but Lawson's leg injury is very serious. Local villagers, Chinese resistance fighters, and foreign missionaries all help the Americans get past the Japanese to safety. But by the time they reach a nearby military base, Lawson has developed gangrene and has to have his leg amputated.
The story concludes a few weeks later with Lawson, now recovering in Washington, D.C., meeting with Doolittle. He tells Lawson that, despite losing his leg, he can still serve in the Army as an aeronautical engineer. Lawson is also reunited with Ellen, but he is afraid that she won't want to be with a cripple. She tells him that she still loves him and always will.