A graduate of the Venezuelan Military Academy, Pérez Jiménez began his political career in 1944, participating in the coups d'état of October 1945 and November 1948. After the second coup he served as a member of the military junta that ruled Venezuela. In December 1952 he became provisional president by designation of the armed forces—an appointment confirmed by the constituent assembly of 1953, which, under his control, elected him to a five-year presidential term (1953–58).

Financed by income from oil royalties, Pérez Jiménez began a vast program of public works, including the construction of highways, hotels, office buildings, factories, and dams. Pérez Jiménez and his associates received a commission from every project. The ubiquitous secret police, the ruthless suppression of opponents, the closing of the university, the silencing of the press, rampant inflation, and the jailing of five priests led the church to ally itself with the opposition parties, the dissatisfied workers, and younger military men who felt excluded from the rewards of the administration. After being forced out of office in January 1958, Pérez Jiménez fled to the United States, reportedly taking with him approximately $200 million.

In 1963 Pérez Jiménez was extradited by the United States to stand trial for embezzlement of government funds. After serving five years in jail, he was released and went to Spain in August 1968. Elected to the Venezuelan Senate in 1969 in absentia, his election was annulled on the grounds that he was not a registered voter in Venezuela. In March 1972 in Madrid he announced his candidacy for president in the forthcoming elections. He returned once more to Caracas in May 1972, but his visit prompted riots in the city, and he returned to Spain.