He migrated with his family to Melbourne in 1881. He left home in 1887 to sell real estate and soon became active in the Australian Natives" Association. In 1893, he was elected to Brunswick Town Council and in 1896 became mayor.
Hume Cook was elected to the seat of East Bourke Boroughs in the Victorian Legislative Assembly in 1894.
He supported to federation of Australia 1897, but came only 19th in the vote for the Victorian delegates to the 1897 Australasian Federal Convention. He supported liberal causes, such as protection and state intervention into wage-fixing and working conditions, but lost his seat in 1900.
He joined the fusion in 1909 in an attempt to hold on to his seat, although its creation ran against his liberal principles. From January 1908 to the defeat of the government in 1908, he was a minister without portfolios in the Deakin ministry.
He chaired a royal commission on postal services from June to December 1908.
The Labor Party campaigned actively against him at the 1910 election and he was defeated by Frank Anstey. He ran unsuccessfully for Maribyrnong at the 1913 election. He was also secretary of the Australian Industries Protection League from 1922 until his death and represented Australian industry at the British Empire Economic Conference in Ottawa in 1932.
Hume Cook was involved with Billy Hughes in the establishment of the Nationalist Party in 1916 and the Australian Party in 1929 and 1930.