The tall American used his biggest weapon, dropping just three points on serve, to secure his 10th ATP title.
It was hardly a fair fight, though, because Baghdatis's movement was hampered from the start by what he said later was an old abductor injury that flared up.
Baghdatis got slower as the match progressed and an injury time-out after the first set did not help matters. He barely went through the motions in the second set but did not forfeit the match.
"I didn’t want to win like that," Isner, 30, said at the on-court victory presentation.
"I hope you’re back healthy and back on tour in just a little bit. You’re a class act and I enjoyed playing you today.
"I feel at home on this court. I play so well here."
Fifth seed Baghdatis, in his first final since 2011, apologised to the crowd.
"That’s not the way I wanted to finish a tournament but my body couldn’t handle it today so I’m really sorry I couldn’t compete 100 percent but I tried my best," he said.
He later told reporters he had been battling the injury since before the ATP event in Nottingham, England, in June, where he forfeited his semi-final.
"I played five matches this week … the good thing is that it’s nothing serious,”
The 30-year-old, a losing finalist at the 2006 Australian Open, has not won an ATP event since 2010.
Isner said he was glad to be back on his best surface after a summer stint on the clay of Europe and English grass.
"It’s my favourite surface, hardcourt like this that bounces pretty high," he said.
(Reporting by Andrew Both in Cary, North Carolina, editing by Ed Osmond/Gene Cherry)
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