The unseeded Indo-Russian pair beat the fourth seeds 6-4 6-4 in what was a repeat of the Indian Wells final three weeks ago in which Sania and Vesnina had come out victors.
Sania and Vesnina held off late surges from the Americans, managing to grab the first set after letting a 5-1 lead close to 5-4.
The second set followed a similar script as Sania and Vesnina let a 4-0 lead close to 4-4. But Vesnina fired a forehand winner to seal it for the pair. This was Sania and Vesnina's fifth event together.
They began with back-to-back quarterfinals at Dubai and Doha before winning the Indian Wells but fell early in Miami.
In Charleston, Sania won her 11th WTA doubles title, while Vesnina lifted her fifth.
"It helps we get along so well. If either one of us isn't playing well, you don't get angry at your friends. We've known each other for really long. We play better every day and understand each other's games better. When the other one isn''t playing as well, the other picks it up," Sania said.
"I think Sania has the best forehand on the tour. I see the eyes of the net player who's guarding the ball from her forehand. They're thinking, ''Oh my God, no, the Mirza forehand!" added Vesnina.
Sania was also lavish in her praise for the Russian, who lost the singles final to Caroline Wozniacki.
"Elena has a lethal backhand and the forehand is my strong shot. Opponents run out of ideas what to do, considering they have only half the court to play in," Sania said.
"I think we've improved our volleys and are more confident too. With confidence you start to poach more and do stuff normal doubles players do. And since we're so heavy off the ground, it's easier for the player at net," she added.