In the present day, scientists in the Arctic uncover an old, frozen aircraft. In March 1942, Nazi lieutenant general Johann Schmidt and his men steal a mysterious relic called the Tesseract,[N 2] which possesses untold godly powers, from the town of Tønsberg in German-occupied Norway.

In New York City, Steve Rogers is rejected for World War II military recruitment due to his various health and physical problems. While attending an exhibition of future technologies with his best friend, Sgt. James "Bucky" Barnes, Rogers again attempts to enlist.

Overhearing Rogers' conversation with Barnes about representing his country in the war, Dr. Abraham Erskine allows Rogers to enlist. He is recruited into the Strategic Scientific Reserve as part of a "super-soldier" experiment under Erskine, Colonel Chester Phillips, and British agent Peggy Carter. Phillips is unconvinced by Erskine's claims that Rogers is the right person for the procedure but relents after seeing Rogers jump on a grenade to save his comrades, unaware that it is a test. The night before the treatment, Erskine reveals to Rogers that Schmidt underwent the procedure prematurely and suffered permanent side-effects.

Schmidt and Dr. Arnim Zola harness the energies of the Tesseract, intending to use the power to fuel Zola's inventions, mounting an offensive that will change the world. Schmidt discovers Erskine's location and sends assassin Heinz Kruger to kill him. With Erskine dead and his super-soldier formula lost, U.S. Senator Brandt has Rogers tour the nation in a colorful costume as "Captain America" to promote war bonds while scientists study him and attempt to reverse-engineer the formula. In 1943, while on tour in Italy performing for active servicemen, Rogers learns that Barnes' unit was MIA in a battle against Schmidt's forces. Refusing to believe that Barnes is dead, Rogers has Carter and engineer Howard Stark fly him behind enemy lines to mount a solo rescue attempt. Rogers infiltrates the fortress of Schmidt's Hydra division, freeing Barnes and the other prisoners. Rogers confronts Schmidt, who removes a mask to reveal a red, skull-like visage that earned him the sobriquet "the Red Skull". Schmidt escapes and Rogers returns to base with the freed soldiers.