Aside from the more powerful engine the Mk. 21 had several notable features:

• The propeller was changed to a five-bladed propeller with a diameter 7 inches greater than that fitted to the Mk. XIV.
• To ensure sufficient ground clearance for the new propeller the undercarriage legs were lengthened by 4½ inches. To improve handling on the ground the undercarriage legs were placed 7¾ inches further apart than before. These modifications presented a problem to the designers because the larger undercarriage did not have enough space in which to retract. They solved this problem with a system of levers that compressed the undercarriage legs by about 8 inches as they retracted, and extended the legs again when they were lowered.
• The armament was standardised to four cannon and no machine guns.

In other respects the first production Mk. 21s used the same basic airframe as the Mk. XIV. However the modifications over the Mk. XIV left the aircraft over sensitive to trimming and it exhibited poor performance in trials in late 1944 and early 1945. This led to a damning report from the Air Fighter Development Unit in which they recommended that, "No further attempts should be made to perpetuate the Spitfire family."

This report caused serious concern for Supermarine as their factory at Castle Bromwich had already been converted to produce Mk. 21s and more were coming off the production lines every day. Luckily the most serious problems were easily solved by changing the gearing to the trim tabs and other subtle control modifications, and the aircraft was cleared for instrument flying and low level flying in trials in March 1945.

It was January 1945 before Spitfire 21s became operational. They had little opportunity to engage the enemy before the war ended, but scored a rare success on 26 April 1945 when two Spitfire Mk. 21s shot up and claimed sunk a German midget submarine which they caught on the surface. With the end of the war most orders for the Mk. 21 were cancelled. Only 120 were completed.