The B-25H Mitchell (NA-98) differed from the G primarily in having a much more powerful armament suite. The nose was fitted with four fixed 0.50-inch machine guns instead of two. These guns were installed in a line across the nose and carried 400 rounds each. A pair of 0.50-inch machine guns were installed in individual blisters on the right hand side of the fuselage, each gun carrying 400 rounds. One of the more controversial changes introduced by the B-25H was the deletion of the co-pilot position. The elimination of the co-pilot's seat, armor plate, and controls resulted in a saving of over 300 pounds of weight. At the position of the copilot, a jump seat for the navigator was provided since his position had now been preempted by the forward-moved dorsal turret.

On production versions of the B-25H, the R-2600-20 engines gave way to the -13. The first production B-25H (serial number 43-4105) was flown for the first time on July 31, 1943 by Bob Chilton. The first B-25H was accepted by the USAAF in August of 1943. Production B-25H aircraft carried a pair of 0.50-inch machine guns in individual blisters on the right hand side of the fuselage. On production B-25H aircraft, the crew was five--pilot, navigator/radio operator/cannoneer, flight engineer/dorsal gunner, midships gunner/camera operator, and tail gunner. The last B-25H was accepted in July of 1944. In China the 341st Bombardment Group received B-25Hs in 1945, some of them serving there until the end of the war. The 1st Air Commando Group assigned to Burma was also provided with the B-25H.