二次世界大戰期間美國研出核子彈頭，在1945年投日本迫使日本投降。
在戰爭勝利，以英國為首的歐洲國，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，與聯平起平坐，引受不了冷戰。美國代的是資本主義和自由民主，而聯則代共産主義和計經濟，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1940年代末期開始的冷戰。自1945年起，美國和聯在許多地區和國，進行一連串代理人戰爭，最先有東德和西德的分裂，來包括朝鮮戰爭，以至六十年代初觸核大戰危機的古巴導彈危機。
冷戰期間，聯大力展太空科技，派出全球首個太空人加加林上太空。美國警覺到與聯的太空競賽上的落，美國政府開始大力培養數學和科學人才，在美國國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.