The big-serving 23rd seed struck 30 aces and broke Bonzi for a fourth time on match point to end the punishing match under the lights at Louis Amrstrong Stadium.
“His level today was incredible, I was not expecting an absolute war,” Kyrgios said in an on-court interview. “That could have gone either way. He was up a break early in the fourth but I played some really risky tennis late in the fourth set to win. I’m just happy to get through.”
In their first career meeting, the pair exchanged breaks in the first set before Kyrgios captured it in a tiebreak and broke early in the second to cruise to a 2-0 lead.
Bonzi responded by taking the third set and went up a break in the fourth before Kyrgios stepped up his game, breaking his serve for a fourth time to set up a third round meeting with American J.J. Wolf, who battled past Alejandro Tabilo 4-6 7-5 6-4 6-3 earlier in the day.
The 37-year-old Isner won his first-round match in straight sets Tuesday. The U.S. Tennis Association announced his withdrawal Wednesday night.
Reuters and The Associated Press contributed to this report.