Patrolling the Irish Sea out of Queenstown, Ireland, Wainwright made several unsuccessful attacks on U-boats, and rescued survivors of several ships sunk by the German craft.

In April 1926, Wainwright was transferred to the United States Coast Guard to help enforce Prohibition as a part of the "Rum Patrol".

The General Board of the United States Navy had called for two anti-aircraft guns for the Tucker-class ships, as well as provisions for laying up to 36 floating mines.

Following exercises near Eastport, Maine, she remained on the New England coast until mid-September when she headed south for gunnery tests and training off the Virginia capes.

Later that month, Wainwright operated out of Newport, practiced torpedo tactics near Vineyard Sound, and visited New York to pick up cargo for the flotilla's tender, Melville.

Steaming via Hampton Roads, Virginia, she reached Culebra Island, near Puerto Rico, on the 14th and conducted war games exercises with the Atlantic Fleet.

Later that month, Wainwright carried Assistant Secretary of the Navy Franklin D. Roosevelt; Brigadier General George Barnett, the Commandant of the Marine Corps; and the Chairman of the Civil Service Commission from Santiago to Port-au-Prince, Haiti.

Following that assignment, Wainwright conducted torpedo exercises, patrols, and power trials near Guantanamo Bay until the beginning of March.

The following morning, in response to the imminent threat of war with Germany, Wainwright began to search for submarines and to patrol Hampton Roads to protect the Fleet and naval bases.

[1] By the spring of 1917, the unrestricted submarine warfare campaign—which Germany had launched at the beginning of February—had so succeeded that the entire Allied war effort was endangered.

[1] Wainwright again briefly patrolled Hampton Roads before heading for the New York Navy Yard on 14 April, and on to Boston, where she arrived two days later, to prepare for overseas duty.

On 24 April, the destroyer departed Boston in company with Wadsworth, Porter, Davis, Conyngham, and McDougal, bound for the British Isles.

On 4 July, a member of the destroyer's crew spotted a purported periscope and soon thereafter others claimed that a torpedo was reported to have passed the ship, 5 feet (1.5 m) astern.

After spending the first two weeks of September in repairs at Birkenhead, near Liverpool, she departed the yard at Laird Basin at about 07:00 on the 14th to return to Queenstown.

Three quarters of an hour into the afternoon watch, she received orders sending her to the scene of a submarine attack against an Allied merchantman some 15 nautical miles (28 km) south-southeast of Helvick Head, Ireland.

Wainwright rang up full speed, made off for the reported location, and began a search for the U-boat in conjunction with a British dirigible and other surface units.

Upon reaching the spot where the submarine had been, the warship located an oil slick and began dropping depth charges which failed to achieve positive results.

[1] The destroyer relieved the lighthouse vessel of the four fishermen and continued the search until dusk, when she headed back to Queenstown to land the rescued men.

Action finally came on the morning of 18 October, when Wainwright again received orders to Helvick Head to hunt for an enemy submarine.

However, upon closer inspection, the object proved to be a derelict carrying the crew of the 77-ton Portuguese schooner Aida, which had been captured by German submarine U-43 and sunk with explosive charges.

[1] Hostilities ended on 11 November 1918, and Wainwright returned home early in 1919 to resume duty with the Atlantic Fleet destroyers.

The Treasury Department eventually determined that the United States Coast Guard simply did not have the ships to constitute a successful patrol.

To cope with the problem, President Calvin Coolidge in 1924 authorized the transfer from the Navy to the Coast Guard of twenty old destroyers that were in reserve and out of commission.

The warship retained her name while serving with the Coast Guard's "Rum Patrol" to suppress the illegal importation of alcoholic beverages.

During each of the two succeeding years—in January 1931 and late in March 1932—she returned to St. Petersburg for a month of target practice and afterward resumed her duties along the New England coast.