For his Canadian partner Nestor, it was a fifth Grand Slam doubles title.
There was hardly anything to separate the pairs in the first three sets, each of which went to a tie-break.
Nestor and Zimonjic opened up a 5-2 lead in the first after a double fault by Mike Bryan, but the American brothers hit back after saving a set point at 6-4 to have a set point of their own at 7-6.
That was saved by the second seeds, who won the next two points to take the set.
The first deuce in the second set did not arrive until the 12th game but once again it went to a tie-break.
This time it was the Bryans' turn to move 5-2 ahead and that set them up to level the match.
'Huge' victory for Nestor and Zimonjic
In the third set Zimonjic had the chance to set up the first break point of the match but somehow netted from close range.
In his next service game the Serb served two double faults which allowed the Bryans to set up the first break point of the match but they could not take it.
Zimonjic received on-court treatment for a stomach upset at 3-2 but it did not affect his performance as two games later he and Nestor forced their first break point of the match.
However Mike Bryan saved it with a 126mph serve and once again the set ended with a tie-break.
For the third time in a row one team opened up a 5-2 lead - this time Nestor and Zimonjic and they took the set on their second set point.
The decisive moment came after two hours 20 minutes of the match when the Canadian/Serbian duo earned the first break of the contest against Bob Bryan's serve to go 2-0 up in the fourth set.
Zimonjic and Nestor were second seeds for this year's Championships
The Bryans earned two breakback points in the next game but they were both saved and that was their last chance.
Although Zimonjic served two double faults when serving for the match, he held his nerve and a perfect delivery clinched victory after two hours 41 minutes.
Afterwards Zimonjic told BBC Sport: "It was just huge to play in front of a crowd like this and with great champions surrounding me in my partner and the Bryans.
"I played them in the final a couple of years ago and lost and it is an amazing feeling to defend the title and to go home undefeated."
Nestor praised his partner, saying: "We came together to play as a team because we thought we had a better chance of winning Grand Slams - and to win back-to-back Wimbledons is unbelievable and a great feeling.
"Coming back here and seeing our name on the plaque from last year was great and I feel fortunate to play with Nenad. He is a great player and we are fortunate to beat the Bryans.
"They are great champions and will be around for a long time."
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