Lithgow commissioned at Sydney on 14 June 1941 under the command of Commander Alfred V. Knight DSC RANR(S).
She began her active career in July 1941 as a unit of the 20th Minesweeping Flotilla sweeping in Bass Strait and around Tasmania. Twenty German mines were swept up by the Flotilla in 1941, Lithgow accounting for one of these, on 14 October.
She had a displacement of 650 tone, she was 186 feet long, 31 feet across the beam and had a draught of 10 feet inches. She was capable of 15 knots, and had a crew of eighty five.
She was armed with one 4 inch gun and three Oerlikon anti-aircraft cannons. She could also be equiped with depth charge shutes and throwers.
With the outbreak of the Pacific War Lithgow temporarily assumed anti-submarine patrols off Sydney, before escorting the first US convoy to Darwin in January 1942.
Escorting convoys from Darwin to Thursday Island occupied Lithgow until September 1942 when she departed Townsville for Port Moresby, escorting a troop convoy of three ships. The remainder of the year was taken up protecting New Guinea convoys.
In December she took part in the landing of troops and equipment at Oro Bay for the Buna campaign.
After a refit, Lithgow began nine months of convoy escort and anti-submarine duty on the Queensland coast.
On the morning of 19 December 1943, Lithgow was diverted from her own convoy escort duties to render assistance to convoy TN 192. Seven of the eight merchant vessels in the convoy, along with one of the escorts had run aground on the Great Barrier Reef. Lithgow, along with HMA ships Gympie, Stawell and Castlemaine, disembarked the troops from the stricken vessels and took them back to Cairns before returning to her own escort duties
1944 began with escort duties to New Guinea, followed by the ship's annual refit at Melbourne. In April Lithgow arrived at Milne Bay to begin a period of ten months escort and anti-submarine operations off New Guinea.
In June and July 1945 she took part in Allied operations in the Solomons, supporting the land forces with a series of bombardments against enemy held territory. Lithgow remained in the Solomons, operating as a minesweeper, until the end of September 1945.
She was present at the Japanese surrender at Rabaul. She ended her active war career when she entered Sydney Harbour on 1 November 1945.
IIn 1946 and 1947 Lithgow operated as a unit of the 20th Minesweeping Flotilla, employed on off New Britain, in the Solomons area and on the Queensland coast. Her seagoing career ended in January 1948 when she arrived at Fremantle, finally paying off on 8 June 1948, having steamed 178,000 miles.
HMAS Lithgow received three battle honours for her wartime service: Darwin 1942, Pacific 1941–45, and New Guinea 1942–44.