The 35-year-old Scotsman fell to 115th-ranked Ymer 7-6 (10/8), 4-6, 6-1 after two hours and 50 minutes at the US Open tuneup tournament.
"I'm excited," said Ymer, who saved four set points in the first set. "A lot left to do but it's a very good start of the American swing."
World number 50 Murray, the 2012 and 2016 Olympic champion, is trying to earn a seeding at the US Open, which he won a decade ago.
"It's still possible," Murray said. "I would just need to have a good run in Canada or Cincinnati really. It's pretty straightforward if I was to make a quarterfinal or a semifinal, which right now -- after a loss like that -- doesn't seem realistic.
"I do feel like if I play very well that I could do that. But I'll need to certainly play better than I did today."
|WASHINGTON, DC - AUGUST 01: Andy Murray of Great Britain returns a shot to Mikael Ymer of Sweden during Day 3 of the Citi Open at Rock Creek Tennis Center on August 01, 2022 in Washington, DC. Rob Carr/Getty Images/AFP |
Seven-time Grand Slam champion Venus Williams, playing her first singles match in nearly a year, was also eliminated in the opening round, falling to Canadian qualifier Rebecca Marino 4-6, 6-1, 6-4.
"It was nice to have the crowd behind me," Williams said. "Definitely a great experience. It's my first match so I didn't think I played well a lot of the times.
"Just trying to shake off some rust. That's just to be expected. All I can do is just play another tournament and play better."
Williams had not played a WTA singles match since falling to Taiwan's Hsieh Su-wei 49 weeks ago in Chicago.
Ymer, who lost his only career ATP final last August in Winston-Salem, will next face 15th seed Aslan Karatsev.
Ymer won 75 percent of his first-serve points, 49-of-65, and smashed 37 winners past Murray, who made only 25 with 35 unforced errors, five more than Ymer.
Murray had a set point in the 12th game of the first set but sent a backhand wide and Ymer held into a tiebreaker.
Murray had three more set points in the tiebreak but Ymer smashed two forehand winners and a forehand volley winner to pull level at 7-7, prompting Murray to toss his racquet in frustration. Ymer, 23, took the set on a backhand volley winner.
"Had chances in the first set to close that out," Murray said. "Didn't get it. Yeah, frustrating."
While Murray clawed back to force a third set, Ymer raced to a 4-0 lead, they exchanged breaks on double faults and Ymer ended the match on a backhand crosscourt winner.
Two-time Grand Slam champion Simona Halep, coming off a Wimbledon semi-final run, beat Spanish qualifier Cristina Bucsa 6-3, 7-5.
"Always the first round is difficult when you change the surface," third seed Halep said. "I know it's going to take time to make the game more solid."
US top seed Jessica Pegula cruised 6-2, 6-2, over US wildcard Hailey Baptiste.
Pegula won the most recent WTA Washington event in 2019 after two missed years due to Covid-19.
"It definitely feels weird," Pegula said. "It's great to be back."
- Edmund wins ATP return -
Britain's Kyle Edmund made a triumphant return to ATP singles after three left knee surgeries and a 20-month layoff by defeating Japanese qualifier Yosuke Watanuki 6-4, 7-6 (10/8).
Edmund, who next faces British 16th seed Daniel Evans, played in his first tour-level singles match since October 2020 at Vienna, a month before his first operation.
"I didn't find it easy today," said Edmund. "I hung in there and I got my reward in the end."