Following the attack on Pearl Harbor, warships were urgently needed in the Pacific and Hughes sailed from Norfolk, Virginia on 18 December 1941, arriving San Diego, California in company with , on 30 December. She departed San Diego on 12 January 1942 as an escort for ships bringing reinforcements to Samoa. "Hughes" then sailed from Samoa as part of a carrier striking force built around carrier "Yorktown". She screened the carrier in strikes on Jaluit, Makin, Mili, and Canton Islands, then supported the combined –"Yorktown" Task Force 17 (TF17), as it attacked Japanese bases at Lae and Salamaua on 10 March 1942. Missing the Battle of the Coral Sea while escorting a tanker carrying fuel to Nouméa, "Hughes" reached Pearl Harbor in time to participate in the Battle of Midway.