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The O/400 was the next step in improving upon the HP O/100 design. Two fuel tanks were moved from the engine nacelles into the fuselage, and a medium-size fuel tank was mounted above these two tanks in the upper section of the fuselage. Hollow spars were mounted in the wings; the undercarriage was fitted with towing lugs; and radiator shutters were now fitted at the factory. The engines were now covered with armour plating. The differential thrust of the two engines was compensated by the central tail fin. The fitting of the new Eagle VIII engines made it possible to increase the maximum bomb load. Besides Handley Page, this bomber was also manufactured by the Royal Aircraft Factory, Boulton and Paul, Metropolitan Carriage Wagon, and Birmingham Carriage Co. By the end of the war, 554 planes had been built in England.

The first mention of this plane in frontline use is dated September 1917. These planes were used to bomb railway stations, supply depots, factories and ports at night. Pilots mentioned that the plane handled nicely and was easy to handle on takeoff; however, they noted that the controls were a little stiff and felt slightly delayed.Planes of this type participated in combat on the Western and Palestinian fronts.