Playing for only the second time at this indoor hard-court tournament on Friday night, the 22-year-old Khachanov needed just an hour and 10 minutes to earn his first win against Zverev in three meetings.
The 21-year-old German, meanwhile, appeared to be struggling with right-shoulder discomfort and was far from his best level.
"I'm just enjoying playing good tennis right now. Especially the past couple of months. After winning Moscow, honestly, in Vienna it was tough for me to play emotionally. I'm playing confidently and playing good tennis right now," the ATP World Tour's official Web site cited Khachanov as saying after his win.
The 18th-ranked Khachanov took charge of the match after a shaky start by both players, while Zverev was woeful on serve in the first set and failed to hold even once in four tries.
The world No. 5 appeared to restore some order by holding his serve twice at the start of the second set, but an in-form Khachanov won the final four games to seal the lopsided victory.
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