In 1900 Malan was elected to the Cape Assembly for the Afrikander Bond, of which he later became leader. In 1908 he resigned from Ons Land and was appointed Minister of Agriculture in John X. Merriman's government. He served until the creation of the Union of South Africa in 1910, when he was elected to the Union Parliament for the South African Party and joined Louis Botha's government as Minister of Education. He also became Minister of Mines (later Mines and Industries) in 1912. He remained in the government after Jan Smuts succeeded Botha in 1919. In April 1920 he also became Minister of Agriculture. He also acted as Prime Minister for eight months while Botha and Smuts were away at the Paris Peace Conference in 1919. After Smuts's government fell in 1924, Malan never again held government office. In 1927 he was elected to the Senate, becoming its President (Speaker) in January 1940. He held this post until his death.
He was appointed to the Privy Council in the 1920 Birthday Honours, entitling him to the style "The Right Honourable".