Keys, 22, cruised past Kaia Kanepi in just over an hour, winning in straight sets to reach her first ever US Open semi-final.
And her win at Flushing Meadows held particular significance as she ensured it would be the first time since 1981 where all four players left in the Grand Slam were American.
Coco Vandeweghe, who she will play in the next round, Venus Williams and Sloane Stephens were the other three women to book their place in the last four.
And despite feeling nervous prior to her clash with Estonian Kanepi, Keys was quick to express her relief and delight at creating history.
“I think it is pretty cool,” Keys said when asked about how she feels about the all-American set up for the semis.
“We were all rooting for each other today and I thought it would be a really special moment and I’m happy I helped everyone out and got my name in there.
The world No. 15 also spoke out about her battles with injury in the last year after having two surgeries on her wrist in just over 10 months.
When asked about her journey to the semi-finals, Keys added: “It was a long way down the road.
“After Paris I flew home, had surgery and I just wanted to have a good year – and I think this is a pretty good year for me.
“I was real nervous. In the car ride over I was definitely feeling it, but once I got out here I felt really good.”