Gasquet used a series of drop shots to take the first set and was also helped when Murray lost his service in the opening game.
Scotsman Andy Murray's long-awaited return to singles play Monday at the Western & Southern Open in Cincinnati didn't go as well as he or his fans might have expected with a 6-4, 6-4 first-round loss to Frenchman Richard Gasquet.
"We were hoping to hold a wildcard until nearer the time and see how it feels", Murray said.
"But I'll maybe play Winston Salem potentially".
After falling behind 2-0 in the second set, Murray came close to breaking Gasquet in the fourth game but failed to do so.
"I felt like I wanted to maybe try and get a couple of matches in before making a decision like that", he said.More news: Cuccinelli Edits Lazarus Poem To Justify 'Public Charge' Rule
Murray, 32, admitted his legs were "a little heavy" after his defeat to Richard Gasquet in Cincinnati and he still needed time to build up his fitness.
Watch the 2016 US Open live on Eurosport and Eurosport Player!
"But I feel a bit disappointed, I feel like I can do better and there are a lot of things I can work and I will go away and I will go away and do that and be hopefully better next time".
"Like when he drop-shotted, there were a few times I didn't even run to the ball, didn't react to it, and that's nothing to do with my hip".
Monday's match was Murray's first since the 2019 Australian Open, weeks before his surgery.
The Briton broke once again in the first game of the third set but then surrendered four successive games before fighting back to 4-4, only for Peterson to eventually emerge as a 6-3 3-6 7-5 victor.More news: Cowboys' Dak Prescott turning down over $30M per season?
Murray has indicated he intends to play in the singles at next month's Zhuhai Championships and China Open.
The other member of the Big Three, Rafael Nadal, withdrew from the Masters event, citing fatigue after he won the Rogers Cup in Montreal on Sunday.
Next up for Kyrgios is a first career meeting with eighth seed Karen Khachanov in the second round on Wednesday.
Also, 14th-seeded Johanna Konta was upset by qualifier Rebecca Peterson 6-3, 3-6, 7-5.
In the women's draw, five-time Grand Slam victor Maria Sharapova moved on to a second-round matchup with top-seeded Ashleigh Barty by knocking off fellow wild card Alison Riske 6-3, 7-6 (4).
American Sam Querrey and Japan's Yodhihito Nishioka were also winners, Querrey outlasting France's Pierre-Hughues Herbert 7-6 (2) 7-6 (1) and Nishioka defeated Australian Jordan Thompson 7-5 5-7 6-4.More news: Minecraft's Super Duper Graphics Pack is canceled
- Jio GigaFiber Plans, Pricing, Launch Date: All You Need to Know
- Taylor Swift Releasing Fourth Lover Song and to Perform on SiriusXM
- Britain Sends Warship To Persian Gulf
- Norway mosque attack: Bruised suspect Manshaus appears in court
- W Series winner Chadwick ready to climb ladder towards F1
- Missing dentures found stuck in throat 8 days after surgery
- Stocks rebound after U.S. agrees to delay tariffs on cellphones, laptops
- WhatsApp's fingerprint unlock feature arrives on Android in latest beta
- Knife-wielding man goes on stabbing rampage in Sydney; body found
- Perisic set to sign for Bayern Munich