Creswell worked as a mining engineer in Venezuela, Asia Minor, Rhodesia and the Transvaal before becoming manager of the Durban Deep Mine, at Roodepoort. At the outset of the Second Boer War in 1899 he was commissioned as a lieutenant in the newly raised Imperial Light Horse. When mining on the Witwatersrand began again, he became General Manager of the Village Main Reef Mine. After strongly opposing Chinese labourers being imported to the Transvaal, he resigned as manager in 1903, going on to take a leading role in the campaign to end the use of Chinese labour and “became the champion of the white labourer”, advocating the use of white labour, and white immigration, as the solution to South Africa's labour problems. At the general election of 1910 he was elected to the House of Assembly of the UnionParliament, representing the new South African Labour Party, of which he was leader from 1910 to 1929. He remained an Assembly member until 1938. He was arrested and imprisoned for a month for his role in supporting miners' strikes in 1913 and 1914. The Smuts government suppression of the strikes influenced Creswell and Labour to develop an alliance with J.B.M. Hertzog and the National Party with Labour joining a National Party-led coalition government as junior partner, resulting in Creswell entering the cabinet. As well as serving as the South African Minister of Defence from 1924 to March 1933, Creswell was simultaneously Minister of Labour from 1924 to 1925 and again from 1929 to 1933. The alliance with the Nationalists eventually led to a split in the Labour Party when Hertzog dropped Labour MP Walter Madeley from the cabinet in 1928 due to his support for the multiracial Industrial and Commercial Workers' Union. Creswell and his supporters remained in government and became known as the "Creswell Labour" faction while Madeley and other Labour MPs joined the Opposition and became known as "National Council Labour" due to their being supported by the Labour Party's national council. In 1933, the Creswell Labour faction dissolved with its members joining the Hertzog's party. Following the 1933 general election, Hertzog formed a coalition with Smuts and his South African Party, with the parties merging to form the United Party, resulting in Creswell being left out of cabinet. He remained a member of the House of Assembly until 1938 when he left politics. In 1935 he was President of the Annual Conference of the International Labour Organization held at Geneva.
