The game will be played at the Honourable Artillery Company’s Artillery Garden in London on Tuesday, Nov 9.
“As a club, we are constantly looking to take top class rugby into new areas – we have taken matches to Wembley Stadium with great success, and now we are taking the game right into the heart of the financial capital of the world,” said Saracens chairman Nigel Wray.
“We look forward to hosting the US national team and enjoying another very special occasion.”
Saracens are currently exploring possible venues in London for a new home ground after Watford Football Club activated a break clause in their lease at Vicarage Road, which is due to run to 2017.
Brendan Venter’s side will play their fifth game at Wembley on Saturday when they host Leinster in the Heineken Cup.
Saracens chief executive Edward Griffiths has dismissed speculation that the club will make an announcement about their Vicarage Road future at half-time during Saturday’s match.