After spending her first year in shakedown and training cruises along the East Coast and in the Caribbean, Blue sailed for the Pacific in August 1938 to become flagship of Destroyer Division 7, Battle Force. She exercised with the Battle Fleet in West Coast waters until April 1940 when she accompanied her division to Pearl Harbor. Except for an overhaul at Puget Sound Navy Yard (February–March 1941) and exercises out of San Diego during April, she remained based at Pearl Harbor until war broke out.
The Japanese attack on Pearl Harbor 7 December 1941 caught Blue in port but she safely made her way to sea with only four officers on board (all Ensigns). She served with the offshore patrol in the approaches to Pearl Harbor during December 1941–January 1942 and then joined Enterprise (CV-6) for the attacks at Wotje, Maloelap and Kwajalein Atolls in the Marshall Islands (1 February 1942) and the Wake Island attack (24 February).
During March–June 1942, Blue escorted convoys between Pearl Harbor and San Francisco and then proceeded to Wellington, New Zealand, where she arrived 18 July. She joined TG 62.2 for the invasion of Guadalcanal (7 August), providing fire-support and screening. Although present, she took no active part in the Battle of Savo Island (9 August).
After patrolling off Nouméa, New Caledonia, (13–17 August), Blue returned to Guadalcanal, arriving 21 August. At 0359, 22 August, while patrolling in Ironbottom Sound, she was torpedoed by the Japanese destroyer Kawakaze. The explosion wrecked Blue’s main engines, shafts and steering gear, as well as killing nine men and wounding 21. Throughout the 22nd and 23rd unsuccessful attempts were made to tow Blue to Tulagi. She was scuttled at 2221 on 23 August 1942 after valiant attempts to save her failed.
Blue (DD-387) received five battle stars for her nine months’ service in World War II.