Sock will face Argentina's Juan Monaco in the final Sunday at River Oaks. The 23-year-old American has won 16 consecutive sets in the event dating to his first-round match last year.
''I love playing in this city, on this court. I love the clay,'' Sock said. ''There's something about that little stadium there, it's a great atmosphere.''
The 32-year-old Monaco, the 2012 winner, beat third-seeded Feliciano Lopez of Spain 6-4, 6-2.
''I'm really happy to be here again in the final,'' said Monaco, an eight-time winner on the ATP Tour. ''I was really focused, consistent from the baseline.''
The 6-foot-10 Isner had treatment on his left knee twice during the match.
''My body is a little beat up,'' Isner said. ''I haven't been healthy in a while. We'll see what I need to do. Got to pay the piper eventually.''
American twins Bob and Mike Bryan won the doubles titles for the sixth time, beating Victor Estrella Burgos of the Dominican Republic and Santiago Gonzalez of Mexico 4-6, 6-3, 10-8 (match tiebreaker). The Bryans have 110 team titles.
''It was a battle from the first point to the last, but we feel like we played our best tennis down the stretch,'' Bob Bryan said. ''It's nice to pull out some close wins after losing a few tight matches to start the season. We're looking forward to building momentum through the clay-court season.''
The victory ended a 12-event drought since Montreal in August.
''It feels great to get over the hump and win No. 110 after a bit of title drought,'' Mike Bryan said. ''There's no better place to do it than in Houston, where we've enjoyed so much success and had unbelievable fan support.''