Zimonjic and Stosur recorded the first set's only break at 4-4 and then held to close it out. They continued their momentum in the second set, breaking at 1-1 and eventually winning three straight games from 3-2 to seal their 6-4, 6-2 victory.
The Serbian-Australian pairing won 27 of 31 first serve points, broke serve three times and fought off the one break point on their own serve.
"With Nenad at the net, with his unbelievable hands and volleys, he can really back up my serving, which makes me feel good and able to relax a little bit more," Stosur said.
"As soon as we got that early break in the second set, we were able to play pretty loose and keep playing well."
Zimonjic and Stosur surrendered just one set en route to their first mixed doubles crown as a duo, that coming against Eric Butorac and Timea Babos in the third round.
"We have played once before here at Wimbledon, but it didn't quite work out as well as this time," Stosur said. "We had a great week together. It was a lot of fun. I'm very thankful that Nenad asked me to play. It was obviously a great tournament for us."
Zimonjic now has five mixed doubles Grand Slams to his name, having also won two Australian Opens and two French Opens.
"She has an unbelievable serve," Zimonjic said. "She can serve any type of serve in any part of the box. She is very solid from the back with big forehands. At the net, she's very comfortable.
"All of those things are really important. The first time I saw Sam was when I lost to her in mixed at the 2005 Australian Open. I said, 'I have to ask to play with her. She's going to be a great partner.' I'm glad I got this chance and I'm glad we're sitting here."