After completion of sea trials, the tanker was transferred to her owners and departed for her maiden trip on January 28, 1922 to Puerto Lobos, a large oil storage facility on the Mexican Gulf coast.

Byron D. Benson continued carrying crude oil between the Mexican ports of Puerto Lobos, Tuxpan and Tampico and New York through the end of September.

[7] The tanker passed through the Panama Canal on October 30 on her first trip to San Pedro and again on her return journey on November 24 with 12,000 tons of oil destined for New York.

For example, she made six round-trip journeys between August 1924 and July 1925 season each time carrying between 10,000 and 12,000 tons of crude oil on her eastward trips.

On January 10, 1942 Byron D. Benson was returning from Port Arthur to Bayonne when around 19:30 in foggy weather she rammed Canadian coastal freighter Continent four miles south of Scotland Lightship, off New Jersey coast.

At 22:47 local time on April 4, when the convoy was about 8 nautical miles (15 km) off the Carrituck Inlet, just past Kill Devil Hills, U-552 fired a single torpedo from approximately 1,000 yards which struck Byron D. Benson on the starboard side amidships, between #7 and #8 holds.

All survivors were safely landed in Norfolk, but because of the running engines Byron D. Benson continued moving and burning for the next three days before finally sinking on 8 April in an approximate position 36°8′57.77″N 75°14′41.57″W / 36.1493806°N 75.2448806°W / 36.1493806; -75.2448806.