It was another ride on the Kyrgios roller coaster, mixing sublime tennis and some on-court humor with swearing and berating of the umpire, smashed rackets and a collapse from a winning position.
A time violation handed down by chair umpire Fergus Murphy was the catalyst for the latest Kyrgios rant, with the Aussie loudly remonstrating Murphy's actions between games, between points and, basically, whenever he felt like it.
Kyrgios requested a toilet break, which Murphy denied, but he left the court anyway, taking two rackets with him. He returned about 20 seconds later with two broken rackets, after smashing them in the corridor beneath the stands.
Back on court, he continued his verbal onslaught against Murphy in the final set, claiming that the umpire was unfair to him every time he officiates his matches.
"Worst f---ing ref ever," he shouted after returning. "The worst ref in the game. ... The worst. Hands down."
While Kyrgios was still capable of wowing the crowd with the occasional winner in the third set, his focus was gone and he conceded a break in the sixth game by attempting a tweener drop volley.
After a double fault handed Khachanov the match 6-7 (3), 7-6 (4), 6-2 and the players shook hands, Kyrgios went at Murphy once again.
"You're a f---ing tool, bro," he said.
Kyrgios then appeared to spit in the direction of the umpire before he shunned the traditional handshake.
Ranked 27th, Kyrgios still appears likely to be seeded for the season's final Grand Slam starting in New York on Aug. 26.
But the temperamental star might face significant fines for smashing two rackets in the vicinity of the court, verbally abusing Murphy and not actually using the bathroom after requesting a toilet break.
"He has a really great talent but sometimes the head not in the right place," Khachanov said. "It was a really difficult match for me. I had to really work it out, how to get the win.
"It's really tough [playing Kyrgios], not only for me but for everybody. You have to try and handle it, then you can have chances to win the match. Always try to stay in there."
Earlier, Australian No. 2 Alex de Minaur posted a significant 7-6 (7-3), 6-4 second-round win over American Reilly Opelka.
The world No. 38 faces Yoshihito Nishioka on Friday, with victory over the Japanese also likely to earn de Minaur a US Open seeding.