When a glorious Monday dawned at Wimbledon, two Americans had a chance to reach the round of 16: the big-serving John Isner and the promising teen, Madison Keys.

By late afternoon, rain had returned, Centre Court’s roof was deployed, and American hopes in the grass-court classic were washed up at the earliest stage in more than a century.

Keys, the lone U.S. prospect remaining in the women’s draw following Serena Williams’s defeat, was unable to take the court for the resumption of her third-round match because of a thigh injury suffered Saturday night, shortly before darkness halted play on the cusp of a second-set tiebreak.

The ninth-seeded Isner was upset by Spain’s Feliciano Lopez in a four-set match that turned on a single break of serve.

According to the International Tennis Federation, it was first time that no American man or woman had reached Wimbledon’s round of 16 since 1911.

If the burden of expectations weighed on Isner, the lone American man currently ranked in the top 50, it sat lightly indeed.

“I didn’t know that. Don’t really care, either,” said Isner, 29, whose mood was as bleak as the weather after his 52-ace performance fell short against the left-handed Lopez, a formidable server in his own right.

Earlier Monday, defending champion Andy Murray marched on, turning back South Africa’s Kevin Anderson, 6-4, 6-3, 7-6 (8-6) in a Centre Court match that started with the retractable roof open and ended with it closed.

And top seed Novak Djokovic, who followed Murray on Centre Court, dismissed Jo-Wilfried Tsonga, 6-3, 6-4, 7-6 (7-5), closing with a lunging backhand service return that all but spewed flames as it ripped past the Frenchman.

But rain was the most formidable protagonist Monday, as it often is at Wimbledon, wreaking havoc on an already backlogged schedule.

Among the favorites affected was Maria Sharapova, bidding to win her second Wimbledon title a decade after claiming her first, at 17. Her fourth-round match against Germany’s Angelique Kerber was postponed until Tuesday, which gives her opponent in a potential quarterfinal, the fast-rising Eugenie Bouchard, an extra day’s rest.

Bouchard, the 20-year-old Canadian and 2012 Wimbledon girls’ champion, burnished her résumé as a bold, big-stakes player with her 7-6 (7-5), 7-5 victory over Alize Cornet, the Frenchwoman who ousted the top-seeded Williams on Saturday.

The 13th-seeded Bouchard is the only woman to reach the quarterfinals of all three majors this season.

Rain also put a damper on the Wimbledon debut of Riverside Park’s Francis Tiafoe, the seventh seed in the junior boys’ event. One of four juniors based at College Park’s Junior Tennis Champions Center to qualify for Wimbledon’s junior tournaments, Tiafoe will try for a third day to complete his first-round match, which was rained out Saturday. He led 5-4 and was about to serve for the first set when rain halted the proceedings a second and final time Monday.

The tournament’s second Monday typically sees all of the men’s fourth-round matches completed. By the close of play, shortly after 9 p.m., half that task was accomplished.

On all courts but Centre Court, play was stopped twice for showers that made the grass too slick for safe competition.

And throughout, as is Wimbledon custom, the tournament’s public-address announcer not only kept spectators informed about the forecast but also expressed condolences, gratitude and a measure of solidarity, saying at one point: “We share in your frustration and disappointment.”

There was plenty of frustration on both sides of the net in Isner’s match against Lopez, who summed up the contest as “not fun.”

There is something interminable about Isner’s matches, the sporting equivalent of calculating the value of pi. At 6 feet 9, Isner blasts a serve that’s virtually unreturnable — even if an opponent guesses correctly which direction it’s heading. But because the American struggles to break serve, nearly every set plays out to a tiebreak. They can be endless, as well, as Isner’s three-day victory over Nicolas Mahut at Wimbledon in 2010 attests, settled 70-68 in the fifth set.

“To play him, it’s always difficult,” said Lopez, credited with 34 aces. “You know, there is no rhythm: a lot of aces, a lot of points where you don’t play.”

Despite his serve, regarded as the most difficult in men’s tennis, Isner has yet to advance beyond Wimbledon’s third round in six attempts. In Monday’s 2-hour 50-minute match, he managed just two break points against Lopez and converted neither.

Asked if he felt he needed to work on his return, Isner sidestepped the question, pointing out how difficult it was to break Lopez.

“The guy is holding serve no matter who he is playing against,” Isner said. “It’s tough.”

The 19-year-old Keys arrived at Wimbledon on a tremendous high, having won her first WTA tournament the previous week at Eastbourne. But she was reduced to tears after injuring her thigh in Saturday’s match before it was suspended for darkness.

She returned to the grounds Monday for the tiebreak that hung in the balance, but needed to strap so much tape on her thigh to stabilize the muscle that she could barely walk. She withdrew after being warned that she risked making the strain worse and is now targeting Washington’s Citi Open for her return.