Lismore departed Sydney for service on the East Indies Station on 21 February 1941 in company with her sister ship HMAS Bathurst. The vessels called at Darwin en route and arrived at Singapore on 26 March. On completion on 7 April of boiler cleaning and minor repairs, the ships took up duty on anti-submarine patrols off Singapore. On 26 May they sailed for Suez via Colombo, the Seychelles and Aden. They arrived at Colombo on 3 June. Shortly afterwards the ships sailed to take up duty with the Red Sea Force.
Thereafter, until mid December 1941, Lismore was employed on East African coastal patrol duty which included, from August to December 1941, patrols in the Gulf of Tadjoura as a unit of the forces employed in maintaining a blockade of French Somaliland. On 16 December 1941 Lismore detached from the Red Sea Force and proceeded for Colombo to join the Eastern Fleet for Indian Ocean escort duty.
From January 1942 to April 1943 Lismore served as an escort vessel for Indian Ocean convoys including duty in the Persian Gulf area in the second half of 1942. On 3 May 1943 she arrived at Aden en route for the Mediterranean where with her sister ships HMA Ships Gawler, Ipswich and Maryborough, she formed the 21st Minesweeping Flotilla. Her service in the Mediterranean, however, was mainly confined to escort duty. She once, in August 1943, proceeded into the Atlantic to form part of the escort of an Alexandria bound convoy. Despite numerous air attacks in the Mediterranean en route to the Atlantic the ship escaped damage.
On 25 September 1943 Lismore departed Suez for Kilindini to rejoin the Eastern Fleet for further Indian Ocean escort duty. For the following fifteen months she was almost constantly at sea protecting convoys moving between India and Africa.