In July 1955, South Vietnamese President Ngo Dinh Diem rejected the nationwide elections agreed to by France and North Vietnam at the Geneva Conference of 1954. The pro-Hanoi Vietcong began a guerrilla campaign in the late 1950s to overthrow Diem's government, which an official Vietcong statement described as a "disguised colonial regime".

In 1963, Buddhist discontent with Diem's pro-Catholic discrimination erupted following the banning of the Buddhist flag and the Hue Vesak shootings. This resulted in a series of mass demonstrations known as the Buddhist crisis. With Diem unwilling to bend, his brother orchestrated the Xa Loi Pagoda raids. As a result, America's relationship with Diem broke down and resulted in coup that saw Diem killed.

Diem was followed by a series of military regimes that often lasted only months before being toppled by another. With this instability, the communists began to gain ground. There were more than a dozen governments before the pairing of Nguyen Cao Ky and Nguyen Van Thieu took control of a junta in mid-1965. Thieu gradually outmanoevred Ky and cemented his grip on power in fraudulent elections in 1967 and 1971.

To support South Vietnam's struggle against the communist insurgency, the United States began increasing its contribution of military advisers. US forces became embroiled in ground combat operations in 1965 and at their peak they numbered more than 500,000. Communist forces attacked most major targets in South Vietnam during the 1968 Tet Offensive, and although their campaign failed militarily, it shocked the American establishment, and caused them to think that the communists could not be defeated. Communist forces supplying the Vietcong carried supplies along the Ho Chi Minh trail, which passed through Laos and Cambodia. US president Richard Nixon authorized Operation Menu, a SAC bombing campaign in Laos and Cambodia, which he kept secret from the US Congress.

Its own casualties mounting, and facing opposition to the war at home and condemnation abroad, the U.S. began withdrawing from ground combat roles according to the Nixon Doctrine; the process was subsequently called Vietnamization. The effort had mixed results. The Paris Peace Accords of 27 January 1973, formally recognized the sovereignty of Vietnam "as recognized by the 1954 Geneva Agreements". Under the terms of the accords all American combat troops were withdrawn by 29 March 1973. Limited fighting continued, before the north captured the province of Phuoc Long in December 1974 and started a full-scale offensive, culminating in the Fall of Saigon on 30 April 1975. South Vietnam briefly came under the nominal rule of a Provisional Revolutionary Government while under military occupation by North Vietnam. On 2 July 1976, North and South were merged to form a Socialist Republic of Vietnam.