Spencer Street is a major street in the central business district of Melbourne, Victoria, Australia. It is named for John Spencer, 3rd Earl Spencer, Chancellor of the Exchequer under Lord Melbourne, the Prime Minister of the United Kingdom.

Running roughly from north to south, Spencer Street forms the western edge of the Hoddle Grid.

Important buildings in Spencer Street include Spencer Street Station and the HM Melbourne Assessment Prison. For many years, Spencer Street was also the location of Melbourne's General Post Office.