After receiving his law degree, Macapagal was admitted to the bar in 1936. During World War II he practiced law in Manila and aided the anti-Japanese resistance. After the war he worked in a law firm and in 1948 served as second secretary to the Philippine Embassy in Washington, D.C. The following year he was elected to a seat in the Philippine House of Representatives, serving until 1956. During this time he was Philippine representative to the United Nations General Assembly three times. From 1957 to 1961 Macapagal was a member of the Liberal Party and vice president under Nacionalista president Carlos Garcia. In the 1961 elections, however, he ran against Garcia, forging a coalition of the Liberal and Progressive parties and making a crusade against political corruption a principal element of his platform. He was elected by a wide margin.
While president, Macapagal worked to suppress graft and corruption and to stimulate the Philippine economy. He placed the peso on the free currency-exchange market, encouraged exports, passed the country’s first land-reform legislation, and sought to curb income tax evasion, particularly by the wealthiest families, which cost the treasury millions of pesos yearly. His reforms, however, were crippled by a House of Representatives and Senate dominated by the Nacionalistas, and he was defeated in the 1965 presidential elections by Ferdinand Marcos.
In 1972 he chaired the convention that drafted the 1973 constitution, but in 1981 he questioned the validity of its ratification. In 1979 he organized the National Union for Liberation as an opposition party to the Marcos regime.