Lewis served in Lord John Russell’s government as Secretary to the Board of Control and later as Financial Secretary to the Treasury. Defeated at the 1852 election, Lewis edited the influential Edinburgh Review. On his return to parliament the new Prime Minister Lord Palmerston made him Chancellor of the Exchequer. His last major role was as Secretary of State for War from which position he successfully led the opposition to calls by Russell and William Gladstone to mediate in the American Civil War. His sudden death in 1863 robbed the Liberal Party of a major figure of whom at least one historian has argued that had he lived it might have been Cornewall Lewis rather than Gladstone leading the Liberal Party.