The new destroyer then transited the Panama Canal on 6 May and steamed north to Washington, D.C., where on 17 May she embarked Rear Admiral Joseph K. Taussig, Assistant Chief of Naval Operations, along with a congressional party, for a cruise down the Potomac River to Mount Vernon.

After a post-shakedown refit at her builders' yard, Worden shifted south to San Diego, reaching that port on 19 September, and commenced four years of operations from there as a unit of Destroyer Squadrons, Scouting Force.

In mid-September Worden—in company with Hull (DD-350) and escorting the aircraft carrier Ranger (CV-4)—voyaged to Callao, Peru, for a visit that coincided with the Inter-American Technical Aviation Conference at Lima.

While Ranger proceeded independently homeward upon conclusion of her visit, the destroyers paused at Balboa, Panama Canal Zone, before returning to San Diego.

Worden worked primarily in the Hawaiian Islands over the next two years, interspersing her time at Pearl Harbor and its environs with regular periods of upkeep on the West Coast.

On the morning of 7 December 1941, during the attack on Pearl Harbor, Worden lay in a nest alongside destroyer tender Dobbin (AD-3), receiving upkeep.

That afternoon, the destroyer joined a task force built around the light cruiser Detroit (CL-8), the flagship of Rear Admiral Milo Draemel.

After having seen Neosho to a safe haven at Pearl Harbor, Worden returned to the open sea on 14 December as part of the covering force moving toward Wake Island.

Worden returned to patrol and escort operations in the Hawaiian Islands; and, while thus engaged with the Lexington task force, twice dropped depth charges on suspected enemy submarine contacts off Oahu on 16 January 1942 and again six days later.

Three days later, when the merchantman SS Snark struck a mine in Bulari Passage (a break in the reefs near Nouméa),[1] Worden went to her assistance, passing a tow line to the sinking ship and pulling her clear of the channel entrance.

Worden headed out to sea on the 15th, in company with the Lexington task force, bound for a rendezvous area southwest of the New Hebrides Islands, where, on 1 May, they joined Rear Admiral Frank Jack Fletcher's TF 17, built around the carrier Yorktown (CV-5).

The destroyer escorted Saratoga as she sailed to Midway and flew off reinforcement groups of Army and Marine Corps aircraft before returning to the Hawaiian Islands for training.

On 9 July, Worden headed for the South Pacific with Saratoga's task force but was temporarily detached on the 21st to escort Platte to Nouméa, reaching that port four days later.

Worden caught up with TF 16 on 3 August and, shortly before daybreak on the 7th, was screening Saratoga as the carrier launched air strikes against Japanese positions on Guadalcanal and Tulagi preparatory to the landings.

During the Battle of the Eastern Solomons, Worden screened the flattop as she launched air strikes in company with Enterprise to sink the Japanese aircraft carrier Ryūjō and damage the seaplane tender Chitose.

Dewey passed a towline to her stricken sister and attempted to tow her free, but the cable parted, and the heavy seas began moving Worden—totally without power—inexorably toward the rocky shore.