Ward had missed five match points before Isner guided a desperate low backhand into the net to end an energy-sapping battle that lasted four hours 56 minutes.
As 7,000 roaring fans leapt to their feet in Glasgow's Emirates Arena, Ward lapped up the applause before falling into the arms of Murray, who had been shouting words of encouragement throughout the contest.
"I'd prefer if I didn't have to play these sort of (long five-set) matches each time," Ward, who saw 39 Isner aces whizz by his racket, said in a courtside interview.
"But this is by far the best atmosphere I've ever been part of.
"Towards the end John started slowing his serve down but it's not just about getting his serve back in, you've got to do something with it.
"I started to get more chances at the end and he was getting fewer on my serve."
Isner is no stranger to being kept on court for hours on end, having beaten Frenchman Nicolas Mahut in an 11 hour, five minute marathon in the first round of Wimbledon in 2010.
But on Friday he trudged off court a beaten man, with a large white towel draped around his shoulders, and knowing that the U.S. now faced an uphill task to reach the quarter-finals of the men's team competition.
(Reporting By Tom Hayward, editing by Pritha Sarkar)
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