He was transferred to USS Enterprise in May 1938, and served with distinction in many battles during World War II, including the Marshall Islands, the Solomons, the Coral Sea, and Midway.

Long, anxious hours ensued as Wyffels circled the disabled ship while repairs were being made; she then escorted the straggler back to her convoy.

From August 1943-April 1945, Wyffels, with occasional interruptions for exercises off the New England coast, conducted 10 more successful circuit voyages escorting convoys to and from North Africa.

In winter, stormy weather and heavy seas slowed the awkward merchant ships and increased the number of stragglers, complicating the task of the escort vessels.

On 13 April 1945, as Wyffels was en route home from what was to be her last wartime Atlantic convoy, the destroyer escort received word that President Franklin D. Roosevelt had died, and she lowered her colors to half mast.

In the following months, she operated off Florida and in the Bahamas, serving as a school ship training student crews in basic gunnery and antisubmarine warfare.

On 23 June 1954, She joined the blockade task force to capture and confiscate the civilian oil tanker Tuapse of the Soviet Union with kerosene passing the high sea of Balintang Channel at 19°35′00″N 120°39′00″E / 19.58333°N 120.65000°E / 19.58333; 120.65000 near Philippines eastbound toward the west Pacific Ocean, whereas the crew were detained in various time frames up to 34 years in captivity and certain deaths.