Muñoz Marín, son of the statesman, publisher, and patriot Luis Muñoz Rivera (Muñoz Rivera, Luis), was educated in the United States, where his father served as resident commissioner (1910–16). After serving as secretary to the commissioner (1916–18), studying law, and writing two books, he returned to Puerto Rico (1926) and edited the newspaper La Democracia, founded by his father. Elected to the Puerto Rican Senate (1932), he aligned himself with advocates of independence from the United States. As a result, he was expelled from the Liberal Party (1937). In 1938 he organized the Popular Democratic Party, which won its first victory in 1940 and made Muñoz Marín president of the Senate, a post he held until 1948.

Changing his mind about independence, Muñoz Marín worked closely with the U.S.-appointed governor, Rexford G. Tugwell, to improve housing, farming, and industrial conditions. His Operation Bootstrap was successful as a program for rapid economic growth. When the United States granted Puerto Rico the right to elect its own governor (1948), Muñoz Marín was overwhelmingly elected and then reelected in 1952, 1956, and 1960. During his governorship, he achieved a lifelong goal in changing Puerto Rico's status to that of a commonwealth. In December 1963 he received the U.S. Presidential Medal of Freedom. He refused to run for a fifth term as governor in 1964, stepping aside to serve once again in the Senate of Puerto Rico.