She reached Norfolk on 27 June and there embarked Second Lieutenant Donald B. Cooley, USMC, and 47 enlisted marines for transportation to Wichita, then in South American waters.
Lawrence P. Coghlan, USMC, ashore, Walke got underway for Pará, Brazil, where she fueled before pushing on for Rio de Janeiro.
Walke took on board mail, freight, and embarked passengers from Wichita before getting underway and steaming via Bahia and Guantanamo Bay to the Boston Navy Yard where she arrived on the morning of 4 September.
In mid-November, she served as the vehicle for degaussing tests under the auspices of the Naval Ordnance Laboratory at Solomons Island, Maryland.
After fueling at San Juan on 6 December, the destroyer got underway on the afternoon of the following day on "Caribbean Patrol" in company with O'Brien.
Rendezvousing with Moffett and Sims off Fort-de-France, Martinique, Walke and O’Brien patrolled the approaches to that port, keeping an eye on the movements of Vichy French warships Barfleur, Quercy, and Béarn, through 14 December.
She departed Newport on 27 July and screened a convoy to Iceland, reaching Reykjavík on 6 August and turning toward Norfolk the same day, her charges safely delivered.
The destroyer subsequently returned to those northern climes in mid-September, after local operations in the Newport-Boston area — reaching Hvalfjörður on 14 September.
She operated in Icelandic waters into late September, before she put into NS Argentia, Newfoundland, on 11 October, en route to Casco Bay, Maine.
Walke began an overhaul at the Boston Navy Yard on 25 November 1941 and completed it on 7 December 1941, the "day of infamy" on which Japan attacked Pearl Harbor and thrust the United States into war in the Pacific.
However, TF 17 remained in Samoan waters for only a short time, for it soon sailed north for the Marshall–Gilbert Islands area to deliver the first offensive blow to the enemy, only eight weeks after the bombing of Pearl Harbor.
Although Admiral Chester Nimitz, the Commander in Chief, Pacific Fleet (CinCPAC), considered the raids "well-conceived, well-planned, and brilliantly executed", the damage they actually caused was not as great as reported; and, outside the boost they gave to American morale, the attacks were only a minor nuisance to the Japanese.
Walke then screened Yorktown as she launched air strikes on Tulagi in the Solomons on 4 May 1942 and later separated from that carrier with the "Support Force" (Australia, Hobart, Farragut and Perkins) to protect the southern mouth of the Jomard Passage.
On the afternoon of 7 May, Japanese Aichi D3A Val dive bombers attacked the formation, but the heavy antiaircraft fire thrown up by the ships caused the enemy to retire without scoring any hits.
On 7 March, Allied intelligence learned that a Japanese surface force, including transports, lay off Buna, Papua New Guinea.
The planes from the two American flattops came in from over the Owen Stanley Mountains and inflicted damage on ships, small craft, and shore installations, before they retired.
Detached to escort Ramsay and Sumner, the destroyer reached Suva, in Fiji, on 19 April and got underway the next day, bound for the Tonga Islands.
Reaching Tongatapu on 22 April, Walke fueled from Kaskaskia before she underwent boiler repairs and loaded depth charges prior to her return to TF 17.
Upon completion of the work on 29 May, the destroyer ran trials in the Brisbane River before being pronounced fit for service and sailed for New Caledonia on 9 June.
The contest soon developed into a logistics race as each side tried to frustrate its opponent's efforts to reinforce and supply his forces fighting on Guadalcanal while doing all in his power to strengthen his own.
Walke's future was to be inextricably tied to the almost daily, and nightly, American air and naval attempts to best the Japanese in their thrusts down New Georgia Sound the strategic body of water which stretches between the two lines of islands which make up the Solomons chain and lead to Guadalcanal.
From the information available in dispatches, the commander of the American task force, Rear Admiral Willis A. Lee, knew of the presence of three groups of enemy ships in the area, one of which was formed around at least two battleships.
Proceeding through the flat calm sea and disposed in column formation with Walke leading, the American ships approached on a northerly course about nine miles (17 km) west of Guadalcanal.
At 0006 on 15 November, Washington received a report that indicated the presence of three ships, rounding the north end of Savo Island, headed westward.
The formations as described steamed on course 150 True between Florida and Savo Islands until approximately 00:20, reducing speed from 23 to 17 knots in search of the reported enemy.
At 00:30 following action of WASHINGTON and South DAKOTA, WALKE opened fire to starboard on visible target believed to be a cruiser with a single raked stack.
//signed WJ Collum Jr., Lt. USN// Japanese shells straddled Walke twice, and then a "Long Lance" torpedo slammed into her starboard side at a point almost directly below mount 52.
Almost simultaneously, a salvo of shells from Nagara, Ayanami, and Uranami hurtled down upon the hapless destroyer, a deluge of steel that struck home with devastating effect in the radio room, the foremast, below the gig davits, and in the vicinity of mount 53, on the after deckhouse.
As Washington, dueling with Kirishima and smaller ships, swept through the flotsam and jetsam of battle, she briefly noted Walke's plight and that of Preston, which had also gone down under in a deluge of shells.
Bombed and strafed by Army, Marine, and Navy planes, including aircraft from Enterprise, the four Japanese ships received the coup de grâce from the Meade that morning, just before the destroyer altered course and picked up the destroyermen from Walke and Preston.