USS Williams was commissioned on 1 March 1919 at the Mare Island Navy Yard, Vallejo, California. After shakedown, Williams and Belknap (DD 251) departed Newport, Rhode Island, on 5 June 1919, bound for the Azores. Arriving at Ponta Delgada on the 11th, Williams proceeded to Gibraltar, where she picked up information pertaining to minefields still extant in the Adriatic, for delivery to the Commander Naval Forces, Eastern Mediterranean. The destroyer's brief tour of duty in this area of the world took her to Spalato, Yugoslavia, Gallipoli, in the Dardanelles, and Trieste, Italy, where she operated as part of the American naval forces keeping watch on the tense local situations there in the aftermath of the World War. After returning to the United States via Spalato and Gibraltar and arriving at New York City on 1 August 1919, Williams was eventually assigned to the Pacific Fleet. The destroyer operated out of San Diego until decommissioned there on 7 June 1922 and placed in reserve.

The German invasion of Poland on 1 September 1939 began hostilities in Europe and President Franklin D. Roosevelt immediately declared America's neutrality. To augment the fleet units already engaged in the Neutrality Patrol hurriedly placed off the eastern seaboard and gulf coast of the United States, the Navy re-commissioned 77 destroyers and light minelayers. Williams was accordingly placed in commission at San Diego on 6 November 1939, Lt. Comdr. Louis N. Miller in command.

Following a refit at Mare Island Navy Yard the destroyer operated in the San Diego area until sailing for Panama on 5 February. Transiting the Panama Canal on the 16th, she lay at Balboa for a brief time. During her stay there, the destroyer "manned the rail" in honour of President Roosevelt, who was then engaged in an informal inspection of the Canal Zone's defenses. Underway soon thereafter Williams arrived at the Naval Operating Base (NOB), Key West, Florida, on 27 February. Over the ensuing months, Williams operated with the Atlantic Squadron of the fleet, conducting neutrality patrols as well as training cruises. While conducting her scheduled operations from Key West, the destroyer took part in short-range battle practices and ship-handling drills, while keeping a weather eye on shipping in her vicinity. In March, she conducted an astronomical survey in the Bahamas. On 9 April, Williams transported a survey party to Palmetto Island in the British West Indies before shifting to Guantanamo Bay, Cuba. After moving back to Key West for a time, Williams departed Florida's waters on 2 June and arrived at New York on 4 June. She conducted two training cruises for embarked Naval Reserve contingents, which kept her busy into the late summer of 1940. After a final refit at the Boston Navy Yard, she departed Charlestown, Massachusetts, on 18 September, bound for Canadian waters, and reached Halifax, Nova Scotia, two days later. As one of the 50 flush-deck destroyers transferred to the British under lend lease in return for leases on important base sites in the Western Hemisphere Williams was selected as one of the six units slated for the Royal Canadian Navy. Soon after her arrival at Halifax on 20 September 1940, she got underway for a brief familiarization cruise for the Canadian crewmen. Williams was decommissioned and turned over to the Canadian government as HMCS St. Clair on 24 September, her name was subsequently struck from the Navy list on 8 January 1941.