Escombe became recognized as the ablest pleader in the colony, and, in 1872, was elected for Durban as a member of the legislative council, and subsequently was also placed on the executive council. In 1880 he secured the appointment of a harbour board for Natal, and was himself made chairman. The transformation of the port of Durban into a harbour available for ocean liners was as a result of his and Cathcart William Methven's work.
In 1888-1889 he defended Dinizulu and other Zulu chiefs against a charge of high treason. For several years he opposed the grant of responsible government to Natal, but by 1890 had become convinced of its desirability, and on its conferment in 1893 he joined the first ministry formed, serving under Sir John Robinson as attorney-general. In February 1897, on Sir John's retirement, Escombe became premier, remaining attorney-general and also holding the office of minister of education and minister of defence.
In the summer of that year he was in London with the other colonial premiers at the celebration of the Diamond Jubilee of Queen Victoria, and was made a member of the privy council. Cambridge University conferred upon him the honorary degree of LL.D. The election that followed his return to Natal proved unfavourable to his policy, and he was succeeded in office, in October 1897, by Sir Henry Binns KCMG. Throughout his life he took an active interest in national defence. He had served in the Zulu War of 1879 in the Durban Mounted Reserve, was commander of the Natal Naval Volunteers and received the volunteer long service decoration. In October 1899 he went to the northern confines of the colony to take part in preparing measures of defence against the invasion by the Boers.
- The Speeches of the late Right Hon. Harry Escombe (Maritzburg, 1903), edited by JT Henderson, contains brief biographical notes by Sir John Robinson and the editor.