The top-seeded American, playing her first tournament since a disappointing Wimbledon campaign in which she was slowed by a virus, got her hardcourt build-up to the US Open off to a good start and will try to carry the momentum into next week's tournament at Montreal.
Williams collected her third Stanford trophy and her fourth title of 2014, after triumphs in Brisbane, Miami and Rome.
But the 17-time Grand Slam champion has struggled in majors this year, failing to make it past the fourth round in the Australian Open, French Open or Wimbledon.
She'll have her last chance of the year to add another major title to her resume at the US Open, which starts at Flushing Meadows on August 25.
"That would definitely make (my year) better," Williams said. "That would be a great thing. But I'm just focused on the next tournament."
Kerber, who saved a match point en route to her semi-final victory over Varvara Lepchenko on Saturday, soared to a 5-1 lead in the opening set.
Trailing 5-2, Williams saved two set points as she broke Kerber to trim the gap to 5-3, part of a run of five straight games that gave her a 6-5 lead.
Williams saved one set point with a screaming forehand cross-court winner before Kerber netted a forehand. The American took the game when Kerber poked a forehand wide.
Williams broke Kerber to love to knot the set at 5-5, and held serve for 6-5 with a game that included a 120 mile-per-hour ace.
"It wasn't easy," Williams said. "I blinked my eye and I was down 1-5. She was playing so well, I was like, 'Oh my gosh, what's going on?'
"I just thought to myself, 'Relax, don't get crazy about it. Don't think about anything but making your shots.'"
Kerber saved a set point in the 12th game as she held serve to force a tiebreaker that an increasingly confident Williams dominated.
Williams broke Kerber to open the second set and led the rest of the way, although she needed four match points to finally put the match away.
"I take away a lot of confidence from this match, knowing that I can play with the best," Kerber said. "I felt I was trying and fighting, being aggressive on every point.
"But I know that Serena plays very good in the important moments. She starts moving better, serving better, hitting the lines. That's a very special thing that she has."
- Tough test looms in Montreal -
Williams can expect to be tested next week in her title defense at Montreal, where she could face Wimbledon finalist and Canadian hope Eugenie Bouchard in the quarter-finals.
After a first-round bye, she could find herself facing Australian Samantha Stosur, who beat her in the 2011 US Open final.
Despite the injury withdrawal of Chinese superstar Li Na, the Montreal field boasts a wealth of big names including Maria Sharapova -- who could meet Williams in the semi-finals -- and Wimbledon champion Petra Kvitova.
Kvitova, seeded second, won the Canadian crown in 2012. In her first tournament since her Wimbledon triumph she is joined in the bottom half of the draw by Agnieszka Radwanska, Victoria Azarenka, Jelena Jankovic and Ivanovic.