The 22-year-old and Japan’s Yui Kamiji beat Dutch defending champions Jiske Griffioen and Aniek van Koot 6-4 3-6 6-3 at Flushing Meadows in New York.
Birmingham-born Whiley became the first Briton to win the same event at all four Grand Slams in the same year.
“I can’t believe it. There’s a mixture of emotions. I felt sick at one point, I felt enjoyment at another,” she said.
“Now it’s a little bit of relief and pure happiness. I think it will sink in later when I can relax and celebrate with the people that I love. I need to call my parents because they don’t know yet.”
After most of the match had been played in stifling heat, the players were forced off court when it began raining heavily with Whiley and Kamiji leading 4-3 in the deciding set.
“I was a bit worried because I’m not good at rain delays, especially when I was just getting into my groove in the third set,” Whiley said.
“But we went down to the locker rooms, played some music and we busted out some moves. It kept us lively and it worked.”
She and Kamiji also hold the Australian, French and Wimbledon titles.
But there was no joy for Scotland’s Gordon Reid in the men’s doubles final as he and Dutch partner Maikel Scheffers lost in a third-set tie-break to top seeds Stephane Houdet and Shingo Kunieda.
Reid and Scheffers fought back from losing the opening set to dominate the second and then had two match points at 6-5 up in the third and deciding set before Houdet and Kunieda won 6-2 2-6 7-6 (7-4).