Salisbury sounded slightly embarrassed to be in the final after he and Krawczyk were given a walkover in the last four but they showed they fully deserved their place by beating Russian duo Elena Vesnina and Aslan Karastev 2-6 6-4 10-5.
It is a second Grand Slam title for Salisbury, who follows in the footsteps of John Lloyd, the winner of the mixed doubles in 1982 with Australian Wendy Turnbull.
Salisbury previously lifted the Australian Open men’s doubles trophy last year with another American, Rajeev Ram, while this is Krawczyk’s first Slam title.
Vesnina and Karatsev were much the better team in the first set but Salisbury and Krawczyk kept pace with their opponents through the second and then took advantage when Karatsev suddenly went off the boil.
Salisbury thought he had served an ace to clinch it and he and Krawczyk sat down in their chairs only to be called back on court by umpire Carlos Ramos, who had decided the British player’s serve was out.
Salisbury argued vehemently with the Portuguese official, and promptly served a double fault when play got back under way, but he held his nerve to clinch a third set point.
And Salisbury and Krawcyzk maintained their momentum through the tie-break, taking their first match point when Karatsev sent a return wide.
Salisbury and Krawcyzk looked stunned and, addressing his partner, the Londoner said: “This has been an incredible week for us and I don’t think we expected this but it’s been so much fun playing with you and thanks for carrying me.”