The win gave the top-seeded American brothers their eighth Grand Slam title and fourth at Melbourne Park, where they also won in 2006 and 2007.
"We feel comfortable here," Mike told reporters after the one-hour-52-minute match at Rod Laver Arena.
"I think Andre (Agassi) called it the happy slam. Seems we're in a good mood coming down here, fresh from an off-season. We like to get a jump to the year."
The Bryan brothers, who defeated India's Mahesh Bhupathi and Mark Knowles of the Bahamas for the title last year, also ended a five-match losing streak against Wimbledon doubles champions Nestor and Zimonjic.
The Bryans appeared to be coasting to an easy victory after wrapping up the first set in 32 minutes, but were broken at 2-1 in the second as Nestor and Zimonjic lifted the pressure.
They steadied in the decider after losing the tiebreak, however, breaking Nestor to take a 3-1 lead and then celebrating victory with a jumping hug.
The Bryans surprised by swapping their usual court positions for the match, a tactic that appeared to work well for them.
"We thought we would try something different. They've kind of had our number. So yeah, could be the way of the future," Mike said.
The 31-year-old Californians are now the second-highest grand slam-winning pair in the open era, behind Todd Woodbridge and Mark Woodforde, who won 12.
"The Woodies are our idols," Bob said. "I imagine if we stay healthy, we might touch that mark. We'd love to keep going as long as possible."
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