He volunteered for Lieutenant Stephen Decatur's expedition into Tripoli Harbor on 16 February 1804 to destroy USS Philadelphia, a United States frigate captured by Tripolitan pirates in the First Barbary War.

After shakedown Killen cleared Port Angeles, Wash. on 19 August 1944, escorted a convoy from Pearl Harbor and arrived at Manus, Admiralty Islands on 14 September.

Killen formed part of the screen for the cruiser USS Nashville carrying General Douglas MacArthur to nearly every island in the chain to give his "I have returned" speech.

in January 1963 to be used as a target ship for missile and gunnery practice off the nearby Puerto Rican island of Vieques where she was eventually sunk/scuttled in a shallow bay in 1975 and still lies today.

Studies and site visits made in 1999 by a Puerto Rican marine archaeologist and the University of Georgia discovered nearly two hundred steel barrels of unknown origin and contents among the wreckage of the Killen.

In 2003–2004, a Virginia-based company called Underwater Ordnance Recovery (UOR), in cooperation with the University of Georgia, was contracted by the Commonwealth of Puerto Rico's Justice Department to again study the ex-Killen wreck.

UOR's final conclusion, issued in March 2004, was that the ex-Killen presented minimal to no environmental danger and should be left alone as it is now serving as an artificial reef for sea life.