Seeking a remarkable 13th title at the clay-court grand slam, Nadal had suggested the conditions and heavier balls he described as "slow and dangerous" could impact his hopes.
He came into Monday's meeting with the world number 83 having only played one tournament since February due to the coronavirus pandemic, losing to Diego Schwartzman in the quarter-finals in Rome.
Neither the balls nor any Nadal rust could prevent him from claiming a 6-4 6-4 6-2 victory, though, Gerasimov's admirable resistance fading after he turned his ankle in the third set.
The first break came Nadal's way courtesy of a deft drop shot and that was enough to claim the first set, which he wrapped up with an ace out wide.
Gerasimov showed impressive athleticism for a man of his 6ft 5in frame but could not find his range when it mattered, and he fired a forehand long to hand Nadal the second set.
The Belarusian looked on course to prolong the inevitable after breaking for the first time to start the third to take a 2-0 lead.
However, Nadal soon erased the deficit and Gerasimov was never the same after receiving heavy strapping on his ankle in a medical timeout following a tumble on the decisive point of the set's fourth game.
Nadal will face world number 236 Mackenzie McDonald in the second round.
The Belarusian saw off Aljaz Bedene, with a 6-4 7-6 (7-4) win carrying him through to the quarter-finals of the Open Sud de France.
Bedene was British number two to Murray heading into Wimbledon in 2016, when the Scot won his third grand slam title, but has since reverted to representing his native Slovenia.
He put up a fight against Gerasimov, who sank Murray in straight sets on Tuesday, but the 28-year-old from Minsk took three of his five break-point opportunities and held his nerve in the tie-break to advance.
The success for Gerasimov sets up a last-eight clash with Spain's Alejandro Davidovich Fokina, who scored a fine 7-5 6-2 win over Polish fourth seed Hubert Hurkacz.
Top seed and world number 13 Roberto Bautista Agut raced to a 6-0 6-3 victory over French qualifier Gregoire Barrere, but Croatian third seed Dusan Lajovic tumbled out, losing to Dennis Novak in straight sets.
At the Singapore Open, second seed John Millman fell by the wayside, the Australian slumping 6-4 6-1 to compatriot Matthew Ebden.
French top seed Adrian Mannarino encountered no such problems, ending the hopes of Roberto Marcora with a 6-3 7-5 win to join Ebden in the quarter-finals.
The 33-year-old, who triumphed in Montpellier in 2010 and 2014, won 7-5 6-3 to become the eighth French champion in the 10 editions of the tournament since it was relocated from Lyon.
Pospisil, who battled past second seed David Goffin to reach only his second ATP Tour final, failed to make the most of four break points against the Monfils serve in an hour and 37 minutes.
At the Pune Open, Jiri Vesely ended a five-year wait to lift a Tour title after overcoming Egor Gerasimov.
Vesely saved match points in his quarter-final and semi-final to book a showdown with Gerasimov, which he won 7-6 (7-2) 5-7 6-3.
"I have to be realistic. I had a lot of luck in the week, saving six match points [across] two matches in a row," he said.
"I think that happens once in a lifetime, maybe, you never know…
"Two matches in a row, especially in the quarter-finals and semi-finals, is really big."
Vesely is the eighth player since 2013 to save match points in two matches en route to winning a Tour event.
Seeking his third title at the event, world number nine Monfils triumphed 7-6 (7-4) 6-2 in 82 minutes against the Serbian.
Monfils saved all three break points against Krajinovic in an impressive victory that maintains France's perfect record of ensuring a home player reaches the final of the Montpellier tournament.
The 2010 and 2014 champion will meet Pospisil on Sunday after the Canadian defeated David Goffin in three sets.
Goffin served for the match in the decider but lost three decisive games in a row as Pospisil triumphed 6-3 1-6 7-5 in two hours and 21 minutes.
At the Pune Open, Australia's James Duckworth was beaten 7-6 (7-2) 6-4 by Egor Gerasimov in the semi-finals.
The Belarusian dropped only five points behind his first serve as he reached a maiden ATP Tour final, where he will face Jiri Vesely.
Vesely saved match points for the second round in a row, outlasting second seed Ricardas Berankis 6-7 (8-10) 7-6 (7-3) 7-6 (9-7) in a draining encounter to secure a first final in nearly five years.
A positive coronavirus test ahead of the Australian Open meant Murray had not played on the main tour ahead of travelling to Montpellier this week.
The three-time major champion, who lost in the final of a Challenger Tour event in Biella earlier this month, revealed on Monday he did not watch the action at the first grand slam of the year "because I wanted to be there myself".
But Murray also suggested practice had gone well in the meantime and he was optimistic of again competing with the world's best.
Tuesday's first-round meeting with Gerasimov brought a bump back down to earth.
The Briton went down 7-6 (10-8) 6-1 to Gerasimov, whose previous outing had been a 6-0 6-1 6-0 humbling at the hands of Melbourne surprise package Aslan Karatsev.
There were no signs of an impending implosion as Murray held his own in the first set, broken in the seventh game but responding instantly to reach a tie-break.
Gerasimov – playing Murray for the first time – converted a fourth set point, though, and his opponent was way off the pace in the second, forced to defend match point just to avoid an embarrassing bagel.
Home hopefuls Lucas Pouille and Gilles Simon were each also eliminated, while eighth seed Jan Lennard Struff went down to compatriot Peter Gojowczyk.
Radu Albot was the only seed in action at the Singapore Open and came through unscathed against John-Patrick Smith, one of three Australian players to depart across Tuesday's four matches at the tournament.
Murray chose to play in the event as a wildcard to improve his world ranking and avoid tougher first-round encounters, such as facing Stefanos Tsitsipas at the U.S. Open, and he recovered from going behind in the opening set to ease through his first-round tie.
Humbert, who is ranked 26th in the world, came into the clash 87 places ahead of the two-time Wimbledon winner but failed to make home advantage count as the Scot dispatched of him in just over two hours.
Karen Khachanov, who is the seventh seed in Metz, avoided a similar first-set scare to overcome Alexandre Muller 4-6 6-1 6-3, while Marcos Giron edged past Arthur Rinderknech 3-6 7-6 (7-3) 6-4.
That win sets up a second-round tie with fourth seed Alex de Minaur, with Alejandro Davidovich Fokina sneaking past Gilles Simon 4-6 (4-7) 7-6 (7-2) 6-2 in Tuesday's other match.
Frenchman Benoit Paire crashed out of the Astana Open to world number 97 Egor Gerasimov as he lost 7-5 6-4.
John Millman, the fifth seed, did not endure similar struggles as he recovered from losing the first set to ease past Dmitry Popko 3-6 6-1 6-4.
Meanwhile, Ilya Ivashka coasted past Elias Ymer 6-2 6-4 in just over 90 minutes to secure his second-round berth in the Czech Republic.
World number 84 Ruusuvuori saved a set point in the first-set tie-break on his way to a 7-6 (8-6) 6-4 victory and will now face Ilya Ivashka for a place in the semi-finals.
There was nearly another upset as home hopeful Alexander Bublik, seeded second, had to recover from a set down to overcome Miomir Kecmanovic 2-6 6-3 7-5.
Carlos Taberner awaits Bublik in the next round after the Spaniard beat Egor Gerasimov 5-7 7-6(5) 7-5.
Kwon Soon-woo and James Duckworth saw off Dusan Lajovic and Filip Krajinovic respectively in straight sets to remain a course for glory.
At the Moselle Open in Metz, meanwhile, Gael Monfils took out Philipp Kohlschreiber 7-6(2) 6-4 to reach the quarter-finals on home soil.
Tournament favourite Hubert Hurkacz made light work of 2016 champion Lucas Pouille with a 6-2 6-3 victory to set up a meeting with Andy Murray in the quarter-finals.
Elsewhere on Thursday, German qualifier Peter Gojowczyk proved too strong for Karen Khachanov and will now face Marcos Giron, who upset fourth seed Alex de Minaur.
