Roddick, seeded seventh, had not lost a set before the final. He earned $400,000 for taking the title.
Fish and Roddick have known each other for years, the former staying at Roddick's house in Florida when the two were juniors in high school.
It was the longest final in terms of games in a Cincinnati-based pro event since 1960.
Roddick improved his record on the U.S. hard courts this summer to 20-1.
"I'm happy for the summer I've had so far, but now I need to regroup, calm down and get ready for a whole new tournament," Roddick said. "I'm not going to probably touch a racket for the next two days."
He remains one of the favorites to win the U.S. Open, which begins Aug. 25, five days before his 21st birthday.
Fish, who became the first unseeded player to advance to the final since 1981 (when unseeded Chris Lewis lost to John McEnroe), was aggressive from the start and had two match points in the 10th game of the third set.
Roddick fought off the first with a near ace Fish barely touched with his racket. Two points later, Fish missed with a forehand that was just wide. Roddick went on to win that game, tying the set at 5-5. In the final tiebreaker, Roddick broke to 3-2 with a passing shot and Fish didn't recovered.
Bob and Mike Bryan won the doubles competition, beating Wayne Arthurs and Paul Hanley, 7-5, 7-6 (5).
Justine Henin-Hardenne beat Russian teenager Lina Krasnoroutskaya, 6-1, 6-0, in the final of the Rogers AT&T; Cup at Toronto for her 12th title.
Henin-Hardenne, the French Open champion ranked No. 3, made quick work of the unseeded 19-year-old Krasnoroutskaya, winning in 54 minutes.
Krasnoroutskaya defeated top-ranked Kim Clijsters in the third round but was unable to solve Henin-Hardenne, who finished with 11 aces. Henin-Hardenne earned $192,000 for the victory. Krasnoroutskaya, ranked 38th, got $97,000.
Unseeded Anna Pistolesi upset fifth-seeded Anastasia Myskina, 6-3, 6-7 (2), 6-4, in the first round of the Pilot Pen tournament at New Haven, Conn. Pistolesi is coming off two consecutive singles titles on clay in lower-tier tournaments at Poland and Finland.
Crystal Robinson made all eight of her shots and scored 19 points to lead the New York Liberty to a 71-54 victory over the Cleveland Rockers in front of 9,462 at Cleveland.
New York stayed in contention for the fourth and final playoff spot in the WNBA's Eastern Conference. The Liberty won for the fifth time in its last eight games and tied Indiana for fifth place at 14-16.
The Liberty will become the first team in WNBA history to play on three consecutive days when it plays host to the Houston Comets tonight in a makeup of a game postponed Thursday because of the Northeast blackout.
New York bounced back from an 84-71 loss to Connecticut at home Saturday to win at Gund Arena for only the third time in 12 games.
Deanna Nolan scored 18 points as the Detroit Shock (22-9) rallied from an early 21-2 deficit to beat the Seattle Storm, 95-86, in front of 7,590 at Seattle.
The Storm (16-14) fell half a game behind Minnesota (17-14) and Sacramento (17-14) in the race for the Western Conference's final postseason berth. The Storm are in fifth place, and only the top four teams make the playoffs.
Ricky Carmichael won the AMA Chevy Trucks U.S. motocross championship race at Spring Creek Motocross Park in Millville, Minn., his seventh victory of the season.
Carmichael's Yamaha teammates, Tim Ferry and Chad Reed, finished second and third in the 250cc race.
Matt Carpenter won his sixth Pikes Peak Marathon at Manitou Springs, Colo., beating nearly 1,000 runners.
Carpenter, 39, covered a lap on the mountain trail course that climbs over 7,000 feet to the 14,110-foot summit of Pikes Peak in 3 hours 43 minutes 46 seconds.
In the women's division, Angela Munge won in 4:19.37 and ended Erica Larson's bid for a fifth consecutive title. Larson was second in 4:22.28.
Chris Dufresne is on assignment.