Isner won seven straight points in the first-set tiebreaker after dropping the first two.
"It probably wasn't the best match as I know he hasn't played in forever and I'm just getting going again," said Isner, ranked 14th in the world. "The best way to prepare yourself for a new year is to get out there and play a match like that. I know there wasn't much riding on the match, but it had that match feel that you can't emulate in practice."
Ferrero, the 2003 French Open champion, surrendered his serve in the eighth game of the second set to enable Isner to serve for the match.
In the first match, Nicolas Almagro beat Alejandro Falla 6-4, 6-1. Almagro won the final two games of the first set and easily finished off Falla in the second.
On Saturday night, recently retired Andy Roddick will face third-ranked Andy Murray.
Roddick, who grew up in nearby Boca Raton, practiced at the venue Friday morning. He's playing his second exhibition since retiring from competitive tennis at the U.S. Open in September.
"I enjoy playing in these things because you still play a little bit, see old friends, not something you're training for weeks at a time," Roddick said. "It's a nice way to stay connected without all the commitments and pressure of the normal tour."