Northmore, second row Alex Coles and fly-half and captain George Ford are the only three players who also started the second Test victory over the Pumas in San Juan.
Leicester’s Jack van Poortvliet gets a start at scrum-half, while Sale pair Bevan Rodd and Asher Opoku-Fordjour are either side of Northampton’s Curtis Langdon in the front row.
Guy Pepper makes his first England start after two impressive cameos off the bench in Argentina, with Harlequins pair Chandler Cunningham-South and Alex Dombrandt completing the back row.
Bristol hooker Gabriel Oghre, who was brought on tour after a Lions call-up for Jamie George and an injury to Theo Dan, is likely to win his first cap off the bench, with backs Charlie Atkinson and Oscar Beard similarly poised to make their Test debuts.
“We know the USA will present a tough challenge,” said Borthwick.
“There’s been a great spirit in the squad throughout this tour. The players have worked hard for each other and pushed standards every day. Those selected this weekend have earned their chance through their effort and attitude.”
England have won all seven of their previous meetings with the United States, most recently prevailing 43-29 in 2021 when, like this summer, a raft of first-choice players were away with the British and Irish Lions.
The United States suffered a 31-24 defeat by Spain in Charlotte last weekend, a loss which caused them to slip to 16th in the world rankings.
The match is being staged in the 20,000-capacity Audi Field in Washington, a venue used by Major League Soccer’s DC United.
Washington is one of 27 cities, including Chicago, New York, Las Vegas and Los Angeles, to have expressed an interest in staging matches when the United States hosts the 2031 and 2033 Rugby World Cups.
