Williams swept the final 10 games and earned her sixth championship in the event Saturday by rallying past Sharapova 4-6, 6-3, 6-0 at the Sony Open.
Sharapova completed a career Grand Slam by winning the French Open last year, but she's now 0-5 in Key Biscayne finals. After playing nearly flawless tennis for an hour, she began to miss with her serve, and Williams dominated rallies down the stretch.
Williams faltered only during the trophy ceremony.
"I felt good today," she told the crowd with the smile. "It's so good to be No. 6 now -- I mean, the six-time -- oh, gosh. Thank you."
Williams has won 11 consecutive matches against Sharapova, whose last victory in the rivalry came in 2004.
"Serena played a great match," Sharapova said. "I'm sure we'll be playing a few more times this year."
At 31, the No. 1-ranked Williams became the oldest female champion at Key Biscayne. She won the tournament for the first time since 2008 and surpassed Steffi Graf, a five-time champion.
Williams lives 2 hours up I-95 in Palm Beach Gardens and considers the tournament her home event.
On Sunday, 2009 champion Andy Murray will play first-time Key Biscayne finalist David Ferrer for the men's title.
The women's final began at high noon in sunny, mild weather, and the quality of play matched the conditions in the early going. The aggressive style of both finalists made for slam-bang points, and the occasional long rally had a near-capacity crowd gasping at the ferocity of the strokes.
Sharapova built her lead by keeping Williams on the defensive, and she kissed the line with a winner on consecutive points to break for a 3-2 advantage in the second set.
Then came the turnaround. Williams began to feast on Sharapova's tentative second serve and broke back at love, then took advantage of two double-faults by Sharapova to break again for a 5-3 lead.
Sharapova made 80 percent of her first serves early on but finished at 63. Williams converted all seven break-point chances and had a 35-13 advantage in winners.
"She definitely pushed me, and I definitely look forward to our next matches," Williams said. "It's going to be really fun for the fans and for us and for everyone."
Williams lost only 10 points in the final set and closed out the victory with a service winner, then was hopping, spinning, waving and grinning in jubilation as the crowd roared.
She became the first No. 1-seeded woman to win the title since she was champion nine years ago. She'll remain No. 1 and Sharapova No. 2 next week.
Sharapova also lost the final in 2005, '06, '11 and '12. Williams' other titles came in 2002, '03, '04, '07 and '08.
"It's tough to lose in the final stage, because you work so hard to get there," Sharapova said. "But the more I give myself this opportunity, the better chance I have of winning."