A member of the Stuart family headed by the Marquess of Bute, Wharncliffe was the son of James Stuart-Wortley, 1st Baron Wharncliffe, and his wife Lady Caroline Elizabeth Mary, daughter of John Crichton, 1st Earl Erne. He sat as Member of Parliament for Bossiney from 1823 to 1830, for Perth from 1830 to 1831 and for the West Riding of Yorkshire from 1841 to 1845. The latter year he succeeded his father in the barony and took his seat in the House of Lords.
Lord Wharncliffe married Lady Georgiana Elizabeth, daughter of Dudley Ryder, 1st Earl of Harrowby, in 1825. They had several children. Wharncliffe died in October 1855, aged 54, and was succeeded in the barony by his eldest son Edward, who was created Earl of Wharncliffe in 1876. Lady Wharncliffe survived her husband by almost 30 years and died in August 1884.