She was named for Boatswain's Mate First Class Reinhardt J. Keppler (1918–1942), who was posthumously awarded the Medal of Honor for "extraordinary heroism" during the Naval Battle of Guadalcanal.

After shakedown along the West Coast, Keppler cleared San Diego, California on 9 October 1947 for training exercises in Hawaiian waters.

Arriving Norfolk, Virginia 15 days later, she immediately commenced intensive anti-submarine warfare (ASW) exercises along the Atlantic Coast.

Keppler sailed to Newport, Rhode Island, her new homeport, for additional hunter-killer operations, arriving on 27 November.

For the next three months she screened her task group during continued carrier air strikes against Communist positions on the Korean mainland.

From 1952 to 1957 Keppler continued her ASW exercises out of Newport and the Caribbean Sea in addition to NATO operations and Mediterranean cruises with the 6th Fleet.

Before returning Newport on 18 March, she visited ports in Colombia, Ecuador, Peru, Chile, Panama, and Cuba.

During September she transited the Suez Canal to the Red Sea, during the United Arab Republic conflict with Jordan.

From 1958 to 1961 the anti-submarine destroyer engaged in concentrated ASW operations along the Atlantic coast and Caribbean NATO exercises, a midshipmen cruise in 1959, and a 6th Fleet deployment in the summer of 1960.

Keppler entered New York Naval Shipyard on 1 March 1961 for a Fleet Rehabilitation and Modernization (FRAM) II overhaul designed to increase her service and effectiveness.

Early in 1967 she returned to "Yankee Station" for plane guard duty and on 28 January assisted in the rescue of another pilot.