Punishing a tired Juan Martín del Potro with his serve and groundstrokes, the lanky American breezed through the first set in 27 minutes after securing an early break.
"I'm playing the best tennis I've played in a very, very long time," Isner said in a courtside interview.
The players held serve in a much-tighter second set until Isner claimed the tiebreak.
Isner, who will become the top-ranked American on Monday, brought up match point with a backhand winner down the line and then clinched with a sublime drop shot.
"I've just continued to keep playing better," Isner said. "I think today was even my best match. Very, very encouraging.
"Physically, I'm super-fresh and I'm ready to go for the finals."
He lost only 11 points on serve in the match, firing 13 aces to four for del Potro, who had upset world number one Roger Federer in the Indian Wells final.
Isner dominated the first set, winning three consecutive games to start the match that included the break of del Potro.
"The first set was pretty easy," the American said. "He's understandably so tired. He's played so many matches and I was a little bit fortunate to get a del Potro who was very low on fuel.
"But I knew the second set would be much tougher."
Although del Potro fought off a break point in the ninth game of the second set, Isner won the first three points in the tiebreak before clinching the match.
