After a tour of ports in the western Mediterranean and the English Channel, Simpson departed Southampton, England, on 1 July 1924 for overhaul at Norfolk, Virginia.

During 1925, unrest in China increased, due to the growth in strength of the Kuomintang forces under Chiang Kai-shek and anti-foreign outbreaks at Shanghai and Canton.

Simpson rescued some missionaries at Deep Bay, China, on 2 and 3 July 1925, and during the next several years, carried out numerous patrols in Chinese waters protecting American lives and property.

The destroyer was stationed at Nanking when Japan launched an air and sea attack on Shanghai at the end of January 1932, and she supported American diplomats in the southern Chinese capital during the critical early days of the crisis, as well as sending important reports to Washington.

After overhaul at Mare Island, Simpson joined Destroyers, Battle Force, at San Diego, California on 28 September 1932 and conducted fleet exercises and training along the U.S. West Coast during the next several years.

During night exercises in a fleet problem off Guantanamo Bay, Simpson collided with Milwaukee, on 7 May 1934, and she underwent repairs at the Philadelphia Navy Yard and summer training at Newport before returning to San Diego on 10 November.

She then commenced training cruises for Naval Reservists, but at the outbreak of war in Europe, she was assigned Neutrality Patrol duty and sailed for the Caribbean on 6 September.

Simpson was part of a support force formed on 18 March 1941, after the signature of the Lend-Lease Act, to protect convoys between America and Britain in the North Atlantic.