"It's moments like this, when you have your good times and your wins, that's what you do it for," said Gesink, the fifth-place finisher in the 2010 Tour de France who broke his leg in four places last September, and whose father died in cycling accident in 2010.
Zabriskie (Garmin-Barracuda) finished second in the event for the fourth time.
Tom Danielson, a Connecticut native who resides in Boulder, Colo., finished third overall for the second straight year, 54 seconds behind.
Rowland Hall graduate Levi Leipheimer, a three-time overall champion, finished in sixth place, 2 minutes, 13 seconds off the lead.
Sagan, who rides for Liquigas-Canondale, claimed his seventh victory of the season and 31st of his career. He swung to the right and bolted to the front seconds before the finish line.
Sagan will compete in the Tour de France for the first time in June and July.
Tom Boonen of Belgium, the current No. 1-ranked cyclist, finished second in the final stage, trailing by a half-length. Gerald Ciolek of Germany placed third.
"The last kilometer was very fast and the last turn was dangerous," said Sagan. "It's good we went by it six times. I went from 150 meters back and just finished first."
The seventh annual event began May 13 in Santa Rosa with a field of 128 representing 16 teams. The 735-mile race, which had 110 finishers, progressed to the San Francisco Bay Area before taking a largely inland route to Southern California.
The race had three leaders, with Sagan winning the first four stages and taking a 40-second margin into the stage 5 individual time trial won convincingly by Zabriskie, a six-time national time titlist.
Gesink, who claimed his only other Tour of California stage in his 2008 debut, assumed the overall lead after winning the seventh and most difficult stage to Mt. Baldy, elevation 6,445 feet.
Defending titlist Chris Horner of Bend, Ore., and the RadioShack-Nissan team, placed eighth overall, trailing Gesink by 2:49. Horner finished sixth in the decisive seventh stage following a long breakaway. Horner also faltered in the individual time trial.
The race also marked the retirement of 39-year-old Robbie McEwen. The Australian sprinting specialist had more than 200 career victories in a 17-year pro career, including 12 stage wins in both the Tour of Italy and Tour de France.