He entered the army, becoming colonel in 1797, but retired in 1801 and devoted himself to politics, sitting in parliament as a Tory for Bossiney in Cornwall till 1818, when he was returned for Yorkshire. His attitude on various questions became gradually more Liberal, and his support of Catholic emancipation lost him his seat in 1826. He was then raised to the peerage as Baron Wharncliffe of Wortley, a recognition both of his previous parliamentary activity and of his high position among the country gentlemen.
At first opposing the Reform Bill, he gradually came to see the undesirability of a popular conflict, and he separated himself from the Tories and took an important part in modifying the attitude of the peers and helping to pass the bill, though his attempts at amendment only resulted in his pleasing neither party. He became Lord Privy Seal in Peel's short ministry at the end of 1834, and again joined him in 1841 as Lord President of the Council.
In 1837 he brought out an edition of the writings of his ancestress, Lady Mary Wortley-Montagu (new ed. 1893). On his death in 1845 he was succeeded as and baron by his eldest son, John Stuart-Wortley (1801-1855), whose son Edward, 3rd baron (1827-1899), best known as chairman of the Manchester, Lincoln & Sheffield railway, converted under him into the Great Central, was created 1st earl of Wharncliffe and Viscount Carlton in 1876; his name was prominently identified with railway enterprise, and became attached to certain features of its nomenclature. He was succeeded as 2nd earl by his nephew Francis (b. 1856).