Break points and chances were few and far between in sultry conditions on Mexico's Pacific coast with each player struggling to find that little bit extra.
Isner won more points on serve and return overall but the temperamental Aussie came through when it mattered, particularly in the third set tiebreak, which he finished with a masterful drop shot from the base line.
He will next meet world number three Zverev, who beat Briton Cameron Norrie 7-6(0) 6-3 in the earlier semi-final.
Zverev, who has won nine ATP titles in the last two years, was just too good for the 23-year old Briton and at one stage won 24 of the 30 points on offer.
News that makes sense
Your trusted source for staying up-to-date with the world around you. Get free daily news updates and analysis, straight to your inbox.
The German, 21, has not lost a set all week in an impressive charge towards the final, his first of 2019.
"It was very tough. It was pretty windy out here, not easy conditions, and his game actually I think fits the wind quite well, so it was not easy," Zverev said.
"I'm just happy to be through. At this stage, you've got to win matches, no matter how. I'm just happy to be in the final."
Kyrgios and Zverev have shared the spoils of their previous six meetings with three victories each, however, Zverev won their previous two matches last year.
(Reporting by Andrew Downie; editing by Sudipto Ganguly)
