Although half the squadron deployed with USS Hornet on the Doolittle Raid, he stayed behind in an 80-man detachment to take delivery of new Grumman TBF Avenger torpedo bombers.

After a short training period out of Naval Air Station Quonset Point, Rhode Island, the detachment flew to California and then took the USS Kitty Hawk to Hawaii.

After a shakedown cruise to Bermuda 28 September to 31 October 1944, Lewis received a week of upkeep at Boston before sailing to Casco Bay, Maine, for a few days training in early November.

With large-scale operations in the Philippines requiring significant logistical support, Lewis spent the rest of the month conducted anti-submarine sweeps along the shipping routes and near Yap Island.

Following shakedown training out of San Diego in May and June, Lewis got underway for Korea on 19 July 1952, making stops at Midway as well as Yokosuka and Sasebo, Japan, before reporting to the Commander, United Nations Blockade and Escort Force on 11 August.

Assigned to the East Coast Blockade and Escort Group, Lewis operated with Republic of Korea (RoK) patrol boats and minesweepers with Commander, Task Element 95.21 embarked.

Starting on 26 August, the destroyer began two months of almost nightly shore bombardment missions against time sensitive targets, firing illumination and high explosive rounds against enemy truck and oxcart convoys, troop concentrations and railroad repair gangs.

Assigned to TE 95.20 on 11 October, Lewis and RoK PC 706 carried out anti-shipping patrols between Wonsan and Hungnam and warned neutral shipping such as Japanese fishing boats out of the coastal defense zone.

1 boiler – killing six fire and boilermen outright and mortally wounding a seventh; Fireman Milton S. Wheeler was awarded the Silver Star for carrying several of his injured shipmates to safety during this attack.

Following hull and machinery repairs at Yokosuka in mid-November, the destroyer escort sailed for home on 17 November, arriving in San Diego via Pearl Harbor on 2 December.

Following an overhaul at Long Beach Naval Shipyard in early 1953, Lewis carried out refresher training and local operations out of San Diego through mid-June.

With the Korean armistice signed just four days previously, Lewis did not conduct combat operations, instead patrolling the Marianas Islands, the Ryukyus and kept watch for communist violations of the truce in the Yellow Sea through the summer and into the fall.

Following an overhaul at San Francisco 1 May – 26 July 1958, the warship's home port was changed to Guam and Lewis sailed to her new station on 14 October, arriving in Apra harbor on 1 November.

Starting in November 1959 she took part in Project Nekton, a series of deep dives in the Mariana Trench by Trieste, a deep-diving research bathyscaphe purchased by the Navy the previous year.

On 23 January, Lewis helped track Trieste with her sonar gear as the bathyscaphe conducted the deepest crewed dive ever undertaken, to the bottom of trench Challenger Deep 35,798 feet (10,911 m) below the surface.