The Mitsubishi design was an all-metal mid-wing cantilever monoplane with retractable landing gear, ventral bomb bay and two radial engines.

Two more Sentais, the 58th and 61st deployed to Manchuria in the summer of 1939 for operations against China, with aircraft from the 61st also being heavily used against Russian and Mongolian Forces during the Nomonhan Incident in June–July 1939.

[6] Losses were high during early combat operations, with weaknesses including a lack of armament and self-sealing fuel tanks, while the aircraft's oxygen system also proved unreliable.

[8][9] This was followed in production by the Ki-21-Ic with provision for a 500 L (130 US gal) auxiliary fuel tank, fitted in the rear weapons bay and one more 7.7 mm (0.303 in) machine gun, bringing the total to six.

[10][9] However, by the attack on Pearl Harbor and the start of the Pacific War, improvements in the ROC Air Force caused losses to mount, and most Ki-21-1a, -1b and -1c were relegated to training or second-line duties.

Front line units from mid-1940 were equipped with the Ki-21-IIa ("Army Type 97 Heavy Bomber Model 2A") with the more powerful 1,118 kW (1,500 hp) Mitsubishi Ha-101 air-cooled engines and larger horizontal tail surfaces.

This became the main version operated by most IJAAF heavy bomber squadrons at the beginning of the Pacific War and played a major role in many early campaigns.

The 3rd, 12th, 60th, and 98th Air Groups, based in French Indochina, struck British and Australian targets in Thailand and Malaya, bombing Alor Star, Sungai Petani and Butterworth under escort by Nakajima Ki-27 and Ki-43 fighters.

To partially compensate, the IJAAF introduced the Ki-21-IIb, with a pedal-operated upper turret with one 12.7 mm (0.50 in) Type 1 machine gun, redesigned cockpit canopies and increased fuel capacity.

When the Ki-21-IIb entered service, the absence of the long dorsal "greenhouse" led Allied observers to mistake it for a completely new type, which was designated "Gwen".