After first-round losses in her last two visits to Flushing Meadows, Krunic looked poised for yet another early exit after Konta, one of eight women here with a chance to leave New York with the world number one ranking, claimed a tight first set.
But the 78th-ranked Serb, who beat Petra Kvitova en route to reaching the last 16 in 2014, dug in to level the match.
In the third set it was Krunic who scored the decisive break to go up 4-2 and then held her nerve as she finished off her opponent on her second match point when Konta sent her return long and wide.
"I feel amazing, happy the way I played the way I fought," Krunic said during her on-court interview. "I had to be at my best from the first point.
"Today it was all about intensity. I am proud of myself, I was tactically able to do the things I had in my head."
It was a stunningly quick end for Wimbledon semi-finalist Konta, who had been expected to be among the title contenders after reaching the fourth round here the last two years.
The 26-year-old certainly had her chances.
After capitalising on all three break chances in the first set, Konta was unable to convert any of her three break points in the second.
"First rounds in every tournament, and especially at slams it can be tricky," said Konta. "She played quite freely, and I think she was able to find her level much quicker and more consistently than I."
(Reporting by Steve Keating in New York; Editing by Pritha Sarkar and Frank Pingue)
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