Lyttelton served in the Second Boer War as commander of the 4th Brigade in South Africa from 9 October 1899. He temporarily became general officer commanding the 2nd Division in February 1900, then commanded the 4th Division, and was involved in the Battle of Spion Kop in January 1900 and the Battle of Vaal Krantz in February 1900, leading to the Relief of Ladysmith later that month. Promoted to lieutenant general for distinguished service in the field on 22 March 1900, Lord Roberts in his despatch referred to Lyttelton as an officer "with great coolness under fire, and considerable tactical knowledge and resource...an excellent commander in the field." He was in command of the troops in Natal until June 1902, when he became Commander-in-Chief of the whole of South Africa following the end of the Second Boer War the previous month. In this role Lyttelton and his wife sought to repair relations with the Boer community. In the South Africa honours list published on 26 June 1902, Lyttelton was knighted as a Knight Commander of the Order of the Bath (KCB).