It was one of the first combat organizations of the United States Army Air Forces to be deployed to the Pacific Theater when elements took part in the June 1942, Battle of Midway using the Martin B-26 Marauder medium bomber.

The 38th Bomb Group was awarded four Distinguished Unit Citations for its combat service in Papua (Buna and Gona, 23 July 1942 to 23 January 1943); New Britain (Cape Gloucester, 24–26 December 43); New Guinea (Jefman-Samate-Sorong, 16–17 June 1944); and Leyte (Ormoc Bay, 10 November 1944).

During the early years of the Cold War, the unit operated in France as a NATO tactical bombardment group flying Martin B-57B Canberras.

The German U-boat threat to Allied shipping earmarked the group for assignment to anti-submarine warfare patrols from a base in South America.

Orders to transfer the group to Savannah AAB, Georgia, as the first step in the process, were rescinded when the United States was drawn into the war on 7 December 1941.

Instead the group remained at Jackson until 18 January when its ground echelon entrained for movement to a port of embarkation at San Francisco, California, where it was quartered in the Cow Palace.

The ground element of the 71st BS moved to Batchelor Field, Darwin, on 1 May to act as a service squadron for the 19th Bomb Group, which had been compelled to evacuate its B-17s from the Philippines by Japanese advances.

The 405th flew to Barksdale Field, Louisiana, to exchange crews with the 17th Bomb Group, which was converting to B-26s because a large portion of its B-25s had been lost on the Doolittle Raid.

Equipped with only ten B-26s and based at Plaine Des Gaiacs Airfield, New Caledonia, it became the first medium bombardment squadron in the South Pacific Area.

Both squadrons conducted search and bombing missions in the Solomon Islands from McDonald Field on Efate during the Guadalcanal campaign, and the 69th staged twice with torpedoes for strikes against the Japanese fleet that never materialized.

During the ferry operation, a navigation error over New South Wales while trying to find Amberley, Queensland caused five bombers of the 405th BS to become lost on 14 August and run out of fuel.

12 Mitchells flew the first combat mission on 15 September 1942, staging through Port Moresby, to bomb and strafe Japanese Army positions and an airfield near Buna, New Guinea.

On 28 September the forward echelon displaced to Laloki airfield, New Guinea, where it continued reconnaissance and occasional bombing missions, while the remainder of the group moved up to Townsville.

[11][n 9] During the month of November 1942, the group staged through Rorona airstrip, flying a limited number of missions while the ground echelon completed its move to New Guinea by sea.

At Durand, as at the five bases which followed, the group lived in dispersed tent cities, was subject to nightly raids on its facilities by Japanese aircraft, and often staged through crude forward strips to extend the range of its combat operations.

Assigned to lead both the group and the 405th BS in an attack on heavily defended Dagua Airdrome, his C-1 strafer was severely hit by enemy fire while at 150 feet.

The two veteran squadrons engaged in a series of large strikes mounted by Fifth Air Force against Rabaul in the latter half of October, attempting to neutralize the Japanese base before Allied landings on Bougainville, scheduled for 1 November.

[11][n 13] After the neutralization of Rabaul, the group attacked airfields on New Britain in preparation for the landing of the U.S. Marines on Cape Gloucester, then shifted on 19 December to bombing of defense positions.

On 15 February 1944 the group attacked Japanese shipping in Kavieng harbor, where a 71st BS B-25 was forced to ditch after being set aflame by antiaircraft fire during its bomb run.

The 670-mile mission, the longest to date by medium bombers in the SWPA, required staging through Hollandia and Wakde airfields and the use of 215-gallon fuel tanks mounted in the bomb bays.

[20] One mission report stated: "Col. (Donald P.) Hall led the formation so low over the drome that plane number 233, piloted by Lieutenant Breneman, was forced to pull up to strafe the operations tower."

[22][n 15] During July and August 1944 the group was taken off operations while it received replacements, trained 63 fresh crews in formation flying, practiced bombing, and exchanged its B-25G and C-1/D-1 models for B-25J aircraft.

[24][n 16] The 38th BG supported the Allied landings on Morotai on the mornings of 15 and 16 September 1944 by conducting low level missions to spray DDT as an anti-malarial measure on the vegetation-overgrown Pitoe Airfield, located just behind Red Beach.

The group, which was awarded its fourth Distinguished Unit Citation for the mission, suffered its greatest loss: seven bombers, three complete crews, and 21 dead or missing.

Flying abreast in four attack waves totaling 22 Mitchells, each squadron lost a bomber in the brief but vicious combat, with two going down in the target area and two others crash-landing at Fourteenth Air Force fields on the Chinese mainland.

On 13 May, after evaluating two months of strikes against Formosan targets, group commander Lt. Col. Edwin H. Hawes conceived a sustained campaign to eradicate all Japanese sugar mill/ethanol refineries on Formosa.

[30][n 25] After its return to Lingayen, it conducted training missions until an advanced party flew to Okinawa on 14 July to prepare for the transfer of the group to Yontan Airfield.

[31] On the morning of 9 August 1945, ten B-25Js led by Col. Hawes attacked the Japanese aircraft carrier Kaiyo (海鷹), beached in Beppu Bay on Kyushu.

[31][n 27] The 38th Bomb Group flew its final combat mission on 13 August 1945, searching for shipping off the east coast of Korea, and the next morning moved its 54 operational bombers back to Morotai to make room for units involved in the imminent occupation.

Okinawa was struck by typhoons on 16 September and 9 October, the latter destroying all tents and structures in the 38th's camp at Yontan, but the bombers were saved by weighting down their wings with sandbags and using full engine power to keep them turned into the wind.