The D.500 and D.501 entered service in July 1935, with the more powerful D.510 joining them in October 1936. They were the primary fighters employed by the Armée de l'Air until their replacement by the Morane-Saulnier M.S.406 in 1939. As of September 1939, the D.500/501 had been relegated to regional defense and training squadrons. At the start of World War II, D.510s were still in operation with three Groupes de Chasse (Fighter Groups), two Escadrilles Régionale de Chasse (Regional Fighter Squadrons in North Africa), and two Escadrilles de Aéronautique Navale (Naval Aviation Squadrons).
In Morocco, one escadrille of D.510s (ERC571) was activated in November 1939. These planes lacked cannon. In May 1940, this escadrille merged with ERC 573 to form GC III/4. This groupe was disbanded by the end of August 1940. At Dakar, one groupe designated GC I/6, remained in service until being replaced by Curtiss H-75s at the end of 1941.
Fourteen D.501s (named D.501L), originally sold to Lithuania, and two D.510s ostensibly intended for the Emirate of Hedjaz saw service in the Spanish Civil War, arriving in mid-1936. When the French government found out about the delivery of the D.510s, they demanded the return of the 12Y engines. The aircraft were then refitted with Klimov M-100s (a Soviet-built copy of the 12Y) from a Tupolev SB bomber. The aircraft served with the Republican forces. The two 510s were posted to the 71st Coastal Defense Group. Neither engaged enemy fighters. In 1938, one was irreparably damaged while landing and the other was destroyed on a runway during a bombing attack.
In 1938, 18 Chinese D.510s saw action against the Japanese, including the defense of Chengdu and the Chinese wartime capital Chongqing.