She operated along the United States East Coast and in the Caribbean with the fleet, carrying out tactical exercises and maneuvers until October 1922.

On 16 December 1922 she rescued approximately 500 survivors of the burning French military transport Vinh-Long about 10 nautical miles (19 km; 12 mi) off Constantinople.

While serving on the United States West Coast, Bainbridge made cruises to British Columbia in Canada, the Alaska, and Hawaii.

During the early part of 1941 she cruised along the northeast coast and between May and November 1941 made three convoy escort voyages to Newfoundland and Iceland.

The United States entered World War II with the Japanese attack on Pearl Harbor on 7 December 1941.