Salisbury, 31, and 39-year-old Ram became the first team to win the Flushing Meadows title three years in a row in the Open era by beating India’s Rohan Bopanna and Matthew Ebden of Australia 2-6 6-3 6-4.
It was a fourth grand slam crown for the duo and denied Bopanna a first major title at the age of 43.
“I think this partnership is really special. It’s been five years and we’ve got pretty close, we know we are going to give it our all until the very end,” said Salisbury.
“We’re just really proud of the effort we put in today.”
Ram dropped serve in the very first game and Salisbury was also broken as Bopanna and Ebden eased to the first set.
With New York still sweltering in 35C temperatures, tournament referee Jake Garner arrived on court to tell the players that the shutters around Arthur Ashe, and then the roof, would have to be closed.
The delay seemed to knock Bopanna and Ebden out of their stride, with Salisbury and Ram securing an immediate break and going on to level the match.
We're just really proud of the effort we put in today— Joe Salisbury
After Ram indulged in his now traditional mid-match sushi snack, they saved three break points for 2-2 in the third and then broke in the next game when Bopanna’s cross-court forehand flew just wide.
Bopanna sportingly gave Salisbury and Ram the point after the umpire missed an Ebden winner brushing his arm on the way through to leave them 0-30 down.
Fittingly, Bopanna hit the winner as he and Ebden came back to hold, but Ram delighted the American crowd by serving out for the title.
Ram paid tribute to Bopanna, saying: “That act of sportsmanship on the court, we’ve been playing the better part of 20 years and I’ve never seen anything like that, especially at a time like that we’d have had no idea. Bops you’re an inspiration.
He added: “Just to be out here, it’s something I could never have thought of in my wildest dreams. I can’t believe we’re here.”