The 11th-seeded pair was in control from early in the opening set to beat young Australian wild-card entries Max Purcell and Luke Saville 6-4, 6-2 in 70 minutes on Sunday at Rod Laver Arena.
It's Ram's second Grand Slam title — he combined with Barbora Krejcikova to win the Australian Open mixed doubles last year. Krejcikova successfully defended that title with Croatia's Nikola Mektic on the same court the previous night.
Ram said he made the call to pull out of the Australian Open mixed doubles when he was ill late last year.
“I didn't have the off-season I would have liked. So I came to Australia very unprepared, to the ATP Cup (in Perth) and didn't feel great,” he said. "Made a call there that it wasn't going to be good for my health or either of my partners, so I just decided that playing the extra event (mixed) wasn't going to be good. Maybe I might have to stick with that decision now for the rest of my career."
Ram, 35, is the first American man to win the Australian Open doubles title since the Bryan brothers in 2013.
This was the Grand Slam final debut for the 33-year-old Salisbury, the first British player to win the title since Jamie Murray in 2016 with Brazil's Bruno Soares.
It was Ram's 58th men's doubles Grand Slam draw and his first finals appearance.
Purcell, 21, and Saville, 25, are the first all-Australian pair to reach their home men's doubles final since Todd Woodbridge and Mark Woodforde in 1998 —before Purcell was born.
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