PARIS -- Rafael Nadal excelled when he needed to most, winning the last two sets against John Isner on Tuesday to advance to the second round at the French Open with a 6-4, 6-7 (2), 6-7 (2), 6-2, 6-4 victory.
The five-time champion, who improved to 39-1 at Roland Garros, played a five-set match at Roland Garros for the first time in seven visits.
"Tough, tough moments for me," Nadal said. "I played too nervous, in my opinion."
Nadal last lost a set at the French Open in 2009, when he was eliminated by Robin Soderling in the fourth round. He had never previously dropped a set in the first or second round.
The top-seeded Nadal is trying to equal Bjorn Borg's record of six French Open titles.
Nadal came into the tournament after losing to Novak Djokovic on clay in finals in Rome and Madrid. But the top-ranked Spaniard is still considered by many to be the favorite at Roland Garros.
That didn't seem to matter -- at first anyway -- to Isner, the man best known for playing in the longest tennis match in history last year at Wimbledon.
Despite losing the first set, the tall American held strong and forced Nadal into a pair of tiebreaks, where his big serve helped him put Nadal on the defensive.
"That's when I started to sort of believe a little bit more," Isner said, "and started to play with more confidence and strut around more out there."
Even Nadal was a bit worried. So was Toni Nadal, Rafael's coach and uncle, who would later say that from his perch in the stands he felt "very, very nervous, because losing in the first round is not too good for us."
But his nephew steeled himself and made zero unforced errors in the fourth set, while Isner made 12.
"I didn't play well in the tiebreak, and I didn't have chances to have the break," Nadal said. "When you play against these kind of players, the pressure is there all the time. You have to play all the time very safe."
Nadal broke Isner for a 2-1 edge in the fourth set and called that "the turning point."
Isner's coach, Craig Boynton, agreed.
"Rafa getting up an early break in the fourth really helped his psyche," Boynton said.
Facing a player having won only one match on the ATP Tour in his career, Murray never seemed at ease on Court Suzanne Lenglen and lost his cool several times during the match, visibly annoyed by his opponent's drop shots.
"It was a tough match. There was no rhythm really to the match," Murray said. "He didn't want to have any long rallies, so he was hitting a lot of drop shots, going for shots. He'd change the rhythm or change the pace of the ball a lot."
Murray, whose best result at the clay-court Grand Slam is reaching the quarterfinals two years ago, acknowledged he was unhappy about the way he moved on the court.
"I hardly won a point when he had drop shots today," Murray said. "I was getting to most of them, just not really doing much with them. So I will do some work on that tomorrow on the practice court."
Murray will play Simone Bolelli of Italy, another qualifier, and still has time to adjust after benefiting from an easy draw. If things go as expected for him, he will take his first real test in the quarterfinals with a potential clash against eighth-seeded Jurgen Melzer of Austria, who won Tuesday.
Playing at a major for only the second time, the 124th-ranked Prodon broke Murray in the ninth game with a backhand drop shot but immediately lost his serve and the set.
Murray then lost only 11 points in the second set and broke Prodon three times in the third.
"I was told going in he's very unpredictable," Murray said. "That's how it was. That's why it was a difficult match and just a quite frustrating one to play, because even though I was in front, all of the points were just really scrappy."
Murray went through a four-match losing streak after the Australian Open but has had a good clay-court season, reaching the semifinals in Monte Carlo and Rome.
He is without a coach after parting ways with Alex Corretja in March. At the French Open, he is getting some help from Darren Cahill -- who used to coach Andre Agassi -- and Sven Groeneveld.
"He's got a lot of experience," Murray said. "And he knows that it's normal not to feel your best in the first match, that it's tricky conditions, and the most important thing is to get through."
The 24th-seeded Querrey entered this year's tournament with an 0-4 career record at Roland Garros.
Querrey's best showing at any Grand Slam tournament were fourth-round appearances at Wimbledon and the U.S. Open.
No. 16 Fernando Verdasco of Spain, No. 18 Gilles Simon of France, No. 20 Florian Mayer of Germany, No. 21 Alexandr Dolgopolov of Ukraine and No. 32 Kevin Anderson of South Africa also advanced, but No. 11 Nicolas Almagro of Spain lost.
Information from The Associated Press was used in this report.