Djokovic has only just returned from a persistent injury to his right elbow and was hoping for a quick match against Simon, who has struggled for form this season and is currently ranked outside the top 30.
And the Serbian, who won this tournament in 2013 and 2015, started promisingly enough. He took the first set 6-3, despite making a number of unforced errors and struggling with his first serve.
When Simon was broken early in the second it looked like Djokovic would be back in the clubhouse with his feet up in little over an hour, but Simon rallied, winning five straight games to take the set in just over 53-minutes.
The Frenchman, formerly ranked World No 6, then smashed a beautiful forehand down the line on break point in the third set to serve for the match. But Djokovic held his nerve, winning the next three games and sealing victory when Simon struck a desperate forehand long.
For Djokovic, victory constituted a job well done regardless of how hard he had been pushed by the Frenchman.
“It was a very difficult match, with many changes of momentum,” Djokovic said after the match.
“It was very tiring for me, the first clay of the season. But this is the start of the Roland Garros build-up.”
It was Simon’s 10th straight defeat against Djokovic and means the 32-year-old is now without a competitive win since February.
And he struggled to hide his disappointment on passing up the opportunity to play either Pablo Carreño Busta or Karen Khachanov in the Third Round, blaming his lack of composure for the loss.
“At 5-4, a lot of work was done to reach that stage. I was not as calm as I had to be. My shots were not as precise... It was a tough moment,” he commented.
“But when you play a match like that, sometimes one is up and the other one is down, and it changes. I played two bad points in a row, and the end came quickly. Of course, I would have preferred to do better at 5-4.”
While Djokovic narrowly avoided an upset, the French number one succumbed to one. Jo-Wilfried Tsonga lived up to his madly unreliable reputation on Tuesday morning when he crashed to a three-set defeat to qualifier Adrian Mannarino.
A two-time semi-finalist at the Country Club and back on court for the first time since the birth of his son, Tsonga had not played since losing his opening match to Fabio Fognini at Indian Wells in early March.
He made a good start, leading 3-0 in the first set, but struggled with Mannarino’s wild range of baseline shots and was broken no fewer than six times in the 6-7 (3-7), 6-2, 6-3 defeat.
The Brits still remaining in Monte Carlo are both in action on Tuesday, with Andy Murray making his competitive return against the big-serving Gilles Müller, who he has never previously lost to.