Jannik Sinner survives challenge from Cincinnati qualifier Alex Michelsen
The world number one Italian, who turns 23 on Friday, has never been past the third round at the American Midwest venue but is hoping to improve on that showing this week.
Victory in just under two hours marked the 25th of the season for Sinner, who is the first man into the third round at the ATP-WTA tournament, the last big test before the August 26th US Open start.
The top seed has not lost before the quarter-final stage of any event since Masters 1000 Shanghai last October.
Teenaged Michelsen went down with 42 unforced errors, his winner count of 14 exactly half of Sinner's total.
"It was a tough match," Sinner said. "I needed to start feeling the conditions and getting used to them.
"I'm very happy to be into the next round. I've struggled here in past years. But today I stayed positive and that helped in the win."
Sinner, who missed the Paris Olympics with tonsillitis and went out last week in the Montreal quarter-finals, said he was not at his best.
"I'm not yet at 100%, but the main goal is the US Open," he said. "I have one week (after Cincinnati) to prepare in the best possible way.
"The matches I can play here will help at the Open."
Ninth seed Stefano Tsitsipas played for the first time since splitting last week with his father as coach, with the Greek turning the tables in dramatic fashion to reach the second round 4-6, 6-4, 6-3 over Jan-Lennard Struff.
Tsitsipas trailed the German by a set and 3-1 but suddenly came alive as his game started to fall into place.
The 2022 Cincinnati finalist finished his victory with a pair of aces.
Tsitsipas ended with 31 winners while Germany's Struff was weighed down by 48 unforced errors, including 10 double faults.
Tsitsipas converted on three of his 14 break-point chances.
"I was in a great state of flow on my serve at the end of the match," Tsitsipas said. "I showed lots of improvement which contributed to my game.
"When I was down I kept on fighting, got the break back and figured out what could work. I took some chances and got myself into the lead.
"I gave a massive push to close it out, mixed up my game and it paid off."
Seventh seed Casper Ruud learned his opening opponent in the second round as Felix Auger-Aliassime booked the spot across from the Norwegian with a 6-3, 6-1 first-round win over US qualifier Aleksandar Kovacevic.
Eighth seed Grigor Dimitrov, the 2017 champion, will start against Fabian Marozsan, who defeated Corentin Moutet 6-3, 7-6(1).
Dane Holger Rune won his first career match here on his third try, defeating former top-10 Italian Matteo Berrettini with a 2-6, 6-1, 6-4 comeback into the second round.
The win ended Berrettini's 10-match win streak, which produced back-to-back clay titles in Gstaad and Kitzbuehel.
In the women's draw, Paula Badosa joined boyfriend Tsitsipas in the second round after defeating Cincinnati local Peyton Stearns 6-2, 7-5.
Washington winner Badosa next plays 13th seed Anna Kalinskaya, a 1-6, 6-2, 6-3 comeback winner against Katerina Siniakova.