With superb performances from Ellesmere Port's Leedham and Stef Collins, the home side made the world's number one team work for their victory.
But a poor second quarter was enough to allow USA to open up a unassailable lead, despite Leedham's best efforts, finishing with more than 20 points to her name.
After a frenetic start, it was advantage Team GB after Leedham and Collins both converted from the three-point line, with Azania Stewart, Julie Page and Natalie Stafford adding to Team GB's 15-8 lead.
USA pulled two points back before the first time-out of the first quarter was called, and Team GB were quickest out of the blocks as Page netted her second.
The visitors looked shell-shocked as GB stretched their lead to 21-10, with Leedham netting consecutive baskets in the space of a minute.
But six points from Moore help draw the visitors level at 21-21, before Lindsay Whalen put the visitors in the lead as they slowly took control, finishing the first quarter at 25-21 ahead.
Manchester-born Page, who had been 100 per cent reliable under the basket, began to miss her shots and the US became more ruthless in attack, with Tina Charles and Moore getting their third two pointers each to make it 31-21.
Leedham - who plays her club basketball in Australia - registered Great Britain's first points of the second quarter two minutes in as her side became more confident in their passing play.
Team GB were restricted to shots outside the arc as the visitors, who kept the home side at bay with strong defence, while stretching their lead through the prolific Moore, who scored 14 points, as they headed into the final time-out of the half with a 45-28 lead.
But two two-pointers from Collins saw GB finish the half strongly, pegging the US team back to a halftime lead of 47-32.
The hosts started the second half well, with Collins, Leedham and Temi Fagbenle, who plays for Harvard University, cancelling out efforts from Tamika Catchings.
Stewart's rebound took Great Britain past the 40-point mark as they tried to match the visitor's strength and intensity on the court.
Collins arrowed a superb effort from outside the arc as Tom Maher's side headed into the first time-out of the third quarter just seven points behind the reigning world and Olympic champions before Moore's sixth two-pointer restored an 11-point lead for Team USA.
Collins, alongside Leedham, was at the heart of everything for Team GB, pushed her side past 50 points, but the visitors began to assert their authority by stretching to a 22-point lead at the end of the third quarter.
Leedham's second success from the three-point line, and two free-throws - bringing her to 20 points in the match - closed the gap to 16 points in the fourth quarter.
But the visitors made sure they saw out the game as they finished with a lead of 25 points in front of a passionate home crowd.