The 23-year-old Italian, who has been struggling with a hip problem, won 7-6 (7-4) 6-2 against American Tiafoe.
After securing the first set on a tie-break, top seed Sinner wrapped up his latest trophy in one hour and 37 minutes.
“It was a very difficult week, tough week. I’m very happy about today’s match,” he said.
Sinner is the youngest men’s champion in Cincinnati since Britain’s Andy Murray won the tournament in 2008 at the age of 21.
He added: “It was very tough mentally. Had such an amazing run here, and I tried to do my best today. We both were quite tired from the semi-finals.”
Sinner started the year by securing his maiden Grand Slam title at the Australian Open in January. He then followed his Melbourne success with final victories in Rotterdam, Miami, and Halle.
After his triumph in Ohio on Monday, Sinner turns his attention to the US Open – the final Grand Slam of the year – which starts on Monday at Flushing Meadows.
“Now, for sure, it’s important to recover, to be ready for New York,” he said.
