Norrie, 23, struggled in the opening stages of his clash with Hungary’s Marton Fucsovics as his opponent broke early and raced into a 3-0 lead.
However, he dug deep and rebounded to force a tie break, that he eventually won in order to take the opening set.
Norrie dominated the second set as broke twice on his way to sealing a 7-6(3) 6-3 victory.
Cameron Norrie of Great Britain celebrates winning the first set against Marton Fucsovics of Hungary in their second round match during day four of the Rolex Monte-Carlo Masters at Monte-Carlo Country Club on April 17, 2019 in Monte-Carlo, Monaco
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It is a remarkable performance from Norrie given that 14 months ago he had never played on clay.
He is closing in on a ranking in the 40s, a new career-high, which would put him top of the British ranking and put him in position to choose the Davis Cup captain later on in the year.
Norrie will face Italy’s Lorenzo Sonego for a place in the semi-finals.
Elsewhere defending champion Rafa Nadal produced a claycourt masterclass to pick apart fellow Spaniard Roberto Bautista Agut 6-1 6-1, as the world number two began his title defence in stunning fashion on Wednesday.
Playing his first match since injuring his knee at Indian Wells last month, Nadal showed no signs of rust as he raced into a 5-0 lead in the first set on Court Rainier III.
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Bautista Agut did get on the board but Nadal clinched the opening set and put his opponent under further pressure with another break of serve at the start of the second.
There was no stopping Nadal who regularly moved Bautista Agut out of position, opening the court up effortlessly with powerful forehand combinations.
After saving three break points at 2-1, Nadal displayed his clinical side at the net to secure a 4-1 advantage and went on to claim a convincing win.
The 11-times Monte Carlo champion extended his winning streak to 16 matches at the tournament and will face Bulgarian Grigor Dimitrov in the third round.
"It was a great start, it's good to be back here," Nadal, the 17-times Grand Slam winner, said.
I've had some great moments on this court, I really enjoy playing here.
"It's not easy to come back from injury, I had to do a lot of mental work as well to be prepared. I tried to play solid, dominate with my forehand when I had the chance."
German hotshot Alexander Zverev showed signs of a return to his explosive best in a 6-1 6-4 win over Canadian teenager Felix Auger-Aliassime.
Third seed Zverev, who lives in Monte Carlo, reached the semi-finals of his 'home' event a year ago, but has endured a difficult 2019 season.
After finishing runner-up to Australian Nick Kyrgios in Acapulco, Zverev has suffered early exits at Indian Wells, Miami and Marrakech.
"This is the first time this season I've felt really healthy," said the 21-year-old.
I've been training well but haven't been able to take that into matches.
"I live just 500 metres from here, I'm comfortable on this court. I'm starting to feel better about my game. I'm really ready for the clay season."
Last year's French Open runner-up Dominic Thiem won 20 of his 23 first-serve points in a commanding display to beat Slovakian Martin Klizan 6-1 6-4.
Greek sixth seed Stefanos Tsitsipas also progressed, defeating Kazakh Mikhail Kukushkin 6-3 7-5