二次世界大戰期間美國研製出核子彈頭，並在1945年投嚮日本迫使日本投降。
在戰爭勝利後，以英國為首的歐洲國傢，元氣進一步大傷。美國儘管在二次大戰中付出沉重代價，由於美國本土未曾遭戰火波及，損失卻是戰勝國中相對地小。美國藉著其經濟和軍事力量，成為世界頭號大國，與蘇聯平起平坐，並引發了冷戰。美國代表的是資本主義和自由民主製，而蘇聯則代表共産主義和計劃經濟，蘇聯的崛起和意識形態的差異，與美國的一套格格不入，雙方衝突造成了1940年代末期開始的冷戰。自1945年起，美國和蘇聯在許多地區和國傢，進行一連串代理人戰爭，最先有東德和西德的分裂，後來包括了朝鮮戰爭，以至六十年代初觸發核大戰危機的古巴導彈危機。
冷戰期間，蘇聯大力發展太空科技，派出了全球首個太空人加加林上太空。美國警覺到與蘇聯的太空競賽上的落後，美國政府開始大力培養數學和科學人才，在美國國傢航空航天局的努力下，於1969年第一次成功派人登上月球。
Following World War II, the United States emerged as one of the two dominant superpowers. The U.S. Senate, on December 4, 1945, approved U.S. participation in the United Nations (UN), which marked a turn away from the traditional isolationism of the U.S. and toward more international involvement. The post-war era in the United States was defined internationally by the beginning of the Cold War, in which the United States and the Soviet Union attempted to expand their influence at the expense of the other, checked by each side's massive nuclear arsenal and the doctrine of mutual assured destruction. The result was a series of conflicts during this period including the Korean War and the tense nuclear showdown of the Cuban Missile Crisis. Within the United States, the Cold War prompted concerns about Communist influence, and also resulted in government efforts to focus mathematics and science toward efforts such as the space race.
In the decades after World War II, the United States became a global influence in economic, political, military, cultural, and technological affairs. Beginning in the 1950s, middle-class culture had a growing obsession with consumer goods.
John F. Kennedy was elected President in 1960. Known for his charisma, he is so far the only Roman Catholic to be President. The Kennedys brought a new life and vigor to the atmosphere of the White House. During his time in office, the Cold War reached its height with the Cuban Missile Crisis in 1962. He was assassinated in Dallas, Texas, on November 22, 1963 by Lee Harvey Oswald.