While brother Andy skipped Flushing Meadows to build up his fitness ahead of his return to top-level singles after hip surgery, Jamie ensured some silverware would be going back to Scotland.
The 33-year-old claimed his seventh grand slam doubles title, and fifth in mixed, with a 6-2 6-3 victory over top seeds Chan Hao-ching and Michael Venus.
A break of the Venus serve, courtesy of a stunning Mattek-Sands return, gave the Glasgow-Minnesota alliance the early initiative.
Murray's instinctive volley then secured the double break and the opening set was wrapped up in 27 minutes.
Mattek-Sands' presence had ensured the backing of the home crowd on Arthur Ashe, and they roared with delight when her backhand return whizzed past Venus on championship point.
The colourful American whipped out her phone to take a selfie with her partner as they celebrated a dominant win.
Murray, who also won this title in 2017 with Martina Hingis, said: "We played amazing the whole two weeks, a lot of great tennis.
"It's easier playing on the big courts, I know Beth loves it, playing in front of lots of people and she played an amazing match.
"She says I'm the yin to her yang. We're really happy to win again."