Stephens was so close to defeat before taking the last three games of a back-and-forth semifinal between two Americans at Flushing Meadows, edging seven-time major champion Williams 6-1, 0-6, 7-5 on Thursday night.
The ninth-seeded Williams is trying to reach her third Grand Slam final of the year.
Keys's journey, against an out-of-sorts Coco Vandeweghe, was much the more straightforward as she completed her 6-1, 6-2 win in just 66 minutes.
"It still doesn't feel real".
Keys has dropped just two sets this tournament and is coming off a match in which she got 72 percent of her first serves in play. "I played pretty well. I didn't feel the best". I don't know how I did it. "Having all the things that were thrown at me this whole year and having some really low moments". "I can't tell you how many times I have sat in this chair and had to hear, you know, how frightful tennis is in America". I am honoured to play at the same time as one of the greats of the game. "I love her to death". Now it will be interesting to see how this latest pair of old friends and rivals react to the pressure of playing for a first major, not to mention the US$3.5 million prize. The semi-final win guarantees Stephens, who was ranked 957 at the end of July, will rocket up the WTA rankings at the conclusion of the tournament.
"Sometimes you have opportunities and sometimes you take them and you don't, but it's not like you get opportunity after opportunity after opportunity in these sorts of matches", Williams said. "So as soon as I kind of felt it get the tiniest bit worse, I just had it wrapped to try and prevent anything from happening". Your guess is as good as mine. "She's so excited to be out on the court again".
Keys looks to make her second Slam semi-final after the 2015 Australian Open, having knocked out fourth-seeded Elina Svitolina in the last-16.
"I just worked my tail off and tried to run every ball down and here we are", Stephens said.
"It required a lot of fight and a lot of grit".
Now 83rd, Stephens is the lowest ranked Slam finalist since unranked Justine Henin at the 2010 Australian Open and the lowest at the US Open since unranked Kim Clijsters won the 2009 title.
But a final break from the American for a 4-2 lead in the second set proved decisive and the match was hers when Pliskova buried a return into the net.
And then came a run to match her best Slam performance from the 2015 Australian Open.
"It was definitely well competed", Williams said.
Williams finished with six double-faults and a total of 51 unforced errors, 24 more than Stephens. I wasn't playing well. "He played during a time where he couldn't just focus on the tennis".
Stephens, 24, is 4-0 in WTA finals, having won titles in 2015 at Washington and previous year in Auckland, Acapulco and Charleston.
Keys had no problem with the No. 20 seed Vandeweghe or with an upper right leg injury that caused her to call the trainer to be taped midway through the second set. When I started my comeback, if someone told me I'd make two Grand Slam semis and a final, I would probably have passed out.
The far more experienced Williams was shakier in the early going, ceding the initial break to trail 3-1 thanks to four consecutive shots that went awry.
It's the first all-American US Open women's semi-finals since 1981 and the first at any Slam since Wimbledon in 1985.
The No. 15 seed beat Kaia Kanepi 6-3, 6-3 to reach the semifinals of a Grand Slam tournament for the second time.
South African Kevin Anderson and Spain's Pablo Carreno Busta meet in the other semi-final.