二次世界大战期间美国研制出核子弹头，并在1945年投向日本迫使日本投降。
在战争胜利后，以英国为首的欧洲国家，元气进一步大伤。美国尽管在二次大战中付出沉重代价，由于美国本土未曾遭战火波及，损失却是战胜国中相对地小。美国藉著其经济和军事力量，成为世界头号大国，与苏联平起平坐，并引发了冷战。美国代表的是资本主义和自由民主制，而苏联则代表共产主义和计划经济，苏联的崛起和意识形态的差异，与美国的一套格格不入，双方冲突造成了1940年代末期开始的冷战。自1945年起，美国和苏联在许多地区和国家，进行一连串代理人战争，最先有东德和西德的分裂，后来包括了朝鲜战争，以至六十年代初触发核大战危机的古巴导弹危机。
冷战期间，苏联大力发展太空科技，派出了全球首个太空人加加林上太空。美国警觉到与苏联的太空竞赛上的落后，美国政府开始大力培养数学和科学人才，在美国国家航空航天局的努力下，于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.