Whitbread was the son of Samuel Whitbread. He was educated at Eton College and University of Cambridge. He was elected Member of Parliament for Bedford in 1790, a post he held for eight years. A campaigner for the abolition of slavery.
He was a close friend and colleague of Charles James Fox. After Fox's death, Whitbread took over the leadership of the Whigs, and in 1805 led the campaign to have Henry Dundas, Viscount Melville, removed from office.