The 23-year-old from England was not even ranked high enough for the qualifying tournament originally but withdrawals got him in and three wins put him in the main draw.
Nishikori was a huge step up but Evans took it brilliantly in his stride, winning four games in a row to take the first set and clinching a 6-4 6-4 6-2 victory in front of a packed crowd on Court 13.
Evans’ run through qualifying here exceeded expectations but was not a surprise given his talent and the great form he has been showing this summer.
Understandably it took Evans a little while to settle into the match and he was broken in the third game, but he levelled at 4-4 and then made it four games in a row to clinch the first set.
Nishikori has had an indifferent summer, but he still would not have expected the world No 179 to cause him such problems.
Evans’ slice backhand was not to the Japanese player’s liking at all, and another ball knifed across the net helped him break serve again to take the second set.
The start of the third was crucial, and Evans dug in to save three break points before edging closer to victory with another break.
Meanwhile, James Blake will retire from professional tennis after the US Open at the age of 33.
An emotional Blake, due to face big-serving Croatian Ivo Karlovic in the first round at Flushing Meadows, made his announcement at a news conference on the opening day of the year’s final major.
“I guess I don’t think I’m catching anyone by surprise by the emails and calls I have gotten in the last 24 hours when I announced I’m having a press conference,” he said.
“No real surprise here. This is my last tournament. I have had 14 pretty darn good years on tour, loved every minute of it, and I definitely couldn’t have asked for a better career.
“For me to think of matches I should have won and to make those as regrets for me has always just seemed greedy.”
Blake, three times a grand slam quarter-finalist — including twice in New York — reached a career high of fourth in the world rankings in 2006 and claimed 10 singles titles and seven doubles crowns on the ATP World Tour.
“I’m really, really excited I have gotten to do this on my terms,” he said. “I had knee surgery a couple of years ago, and if that had been the end it would have been a little more disappointing to me to end it without going out the way I am now, where still just two weeks ago I beat a guy top 20 in the world.
“I know I have the capability of still playing at that level at times. It’s just not with the same consistency I was able to four or five years ago when I felt like every week was an opportunity to win a tournament. I don’t feel like that as much any more.
“I need to leave. I want to leave on my own terms. I’m happy doing that right now.”
He added: “The competition is something I will miss. I will miss pressure-packed moments, break points, set points, match points, crowd getting into it. But I’m so, so fortunate to have a life after this that I’m looking forward to with my wife, with my family.”