The World No 1 and 2019 French Open champion went down in three sets, losing 6-3 2-6 3-6 in one hour and 37 minutes.
Barty, who headed into the clash on the back of a 15-match winning run, was one of the leading favourites to claim the women’s title here at the All England Club.
But after dropping her first set of the tournament to Riske, who spent over four hours longer on court in the first week, the Australian was unable to recover.
USA’s Riske, who has also knocked out Donna Vekic and Belinda Bencic in a giant-killing run, is through to the quarter-finals of a slam for the first time, where she could face Serena Williams.
Barty began the match with four straight aces and hit 12 in all yet one of her biggest weapons was also an Achilles heel, with the Australian struggling to land her first serve.
In the second set her first-serve percentage was down at 40 and she paid the price, with Riske's flat yet precise ground strokes causing Barty all sorts of problems.
For the first time the 23-year-old looked a little flustered, and she had to save two break points to hold for 3-3 in the decider.
The pressure told in her next service game, though, as Riske sent yet another winner down the line to break, and a final backhand wide from Barty brought the curtain down on her campaign.
Additional reporting by PA
Join our new commenting forum
Join thought-provoking conversations, follow other Independent readers and see their replies