Isner calls it quits after US Open loss to Mmoh
Isner added 48 more aces to his record tally, starting strongly to win the first two sets before the physical nature of the contest took its toll on the towering American.
Mmoh grew in confidence after winning the third set tiebreak and rode an early break in the fourth set to force a decider.
Isner had match point at 5-4 in the fifth but Mmoh was able to serve his way out of trouble and levelled with a drop shot.
Fittingly for Isner, who was involved in the longest professional match ever, his final set came down to a tiebreak and a stick volley at the net gave him a 4-2 lead that brought the crowd to their feet.
Mmoh refused to back down, however, completing the comeback when Isner's shoestring volley landed in the net.
"Yeah, it's tough. I like to think I work as hard as I can," an emotional Isner said during an on-court interview before his voice trailed off with emotion.
"This is why I worked as hard as I have my whole life to play in atmospheres like this and of course I may not win them all as we know, just like today," he added.
"But to play in front of this crowd and have the support I had is pretty special so thank you."
Isner turned pro in 2007 and reached a career high of world number eight. He won 16 singles titles, the biggest being the Miami Open crown in 2018, his most successful season.
He won the longest professional tennis match in history against Frenchman Nicolas Mahut at Wimbledon in 2010, which lasted 11 hours and 5 minutes and took place over three days.
The All-England Club was also the site of his best result at a Grand Slam tournament, reaching the semi-finals in 2018. He twice made the US Open quarters, in 2011 and 2018.
Isner is still in action in doubles at the US Open with fellow American Jack Sock (30), who has also said he will retire after the tournament.