He was born in London and succeeded to the baronetcy in 1823. At Cambridge he fought a duel with his tutor, and for some time studied abroad. On the passing of the Reform Act of 1832 he was returned to parliament for the eastern division of Cornwall, to support the ministry of Lord Grey. Through Charles Buller he made the acquaintance of Grote and James Mill, and in April 1835 he founded, in conjunction with Roebuck, the London Review, as an organ of the Philosophic Radicals. After the publication of two volumes he purchased the Westminster Review, and for some time the united magazines were edited by him and J. S. Mill.
From 1837 to 1841 Sir William Molesworth sat for Leeds, and acquired considerable influence in the House of Commons by his speeches and by his tact in presiding over the select committee on transportation. But his Radicalism made little impression either on the house or on his constituency. From 1841 to 1845 he had no seat in parliament. In 1845 he was returned for Southwark, and retained that seat until his death. On his return to parliament he devoted special attention to the condition of the colonies, and was the ardent champion of their self-government. In January 1853 Lord Aberdeen included him in the cabinet as First Commissioner of Works, the chief work by which his name was brought into prominence at this time being the construction of the new Westminster Bridge; he also was the first to open Kew Gardens on Sundays. In July 1855 he was made colonial secretary, but he died on the 22nd of October.