Norrie had not secured a win against a top-20 player since January 2024 and had previously lost all four encounters with Medvedev, including their recent match in Rome earlier this month.
The world number 81 began the match explosively but had to endure a resurgence from Medvedev, who oscillated between frustration and focus as he forced a fifth set.
Norrie fought back from a break down in the crucial final set, ultimately winning 7-5, 6-3, 4-6, 1-6, 7-5 in just under four hours.
Meanwhile, Sonay Kartal progressed to the third round, joining Emma Raducanu and Katie Boulter after a powerful victory over Erika Andreeva in her French Open debut.
This marks the first time since 1973 that six British players have reached the second round at Roland Garros.
Medvedev had the chance to serve for the match at 5-4 in the final set but was unable to fend off Norrie, who then took control by winning three consecutive games to secure the victory.
Norrie had also come back from a break down in the first set and remained composed as Medvedev vented at his box during the first two sets.
After a lengthy forehand from Medvedev signaled his defeat, Norrie celebrated by tossing his racquet into the air.
“There wasn’t much on my mind at match point,” Norrie, 29, reflected. “I sensed he was a bit hesitant, but honestly, it was a wild match. I feel I deserve a diploma for beating Medvedev, considering he had won the last four encounters. It was an unbelievable match.”
Norrie is set to face Argentine lucky loser Federico Gomez for a spot in the third round.
Medvedev often expresses that clay is not his preferred surface—but that does not diminish Norrie’s performance, which was exceptional.
Norrie demonstrated impressive depth in his shots and powerful forehands, effectively engaging in rallies against the defensive Medvedev and returning serves decisively.
After going down a break in the first set, Norrie seized upon Medvedev’s nerves while he was serving for the set— a mistake he would repeat at the match’s conclusion.
After winning the first set, Norrie raced to a 4-0 lead in the second while Medvedev was seen shouting at himself and his coach in French, frequently animatedly gesturing to his box.
Norrie’s courageous striking earned him a two-set lead before Medvedev regained his focus, shedding the theatrics and speeding through two sets to push the match to a decisive fifth.
After breaking Norrie in the third game, the momentum shifted to Medvedev, but an error-filled service game while aiming for victory allowed Norrie to regain the upper hand.
Norrie then held his serve confidently and, by stepping into the court to apply pressure on Medvedev, managed to steer clear of a match tie-break.
In men’s doubles, British sixth seeds Lloyd Glasspool and Julian Cash rallied to defeat Australia’s Rinky Hijikata and Serbia’s Miomir Kecmanovic 4-6, 6-2, 6-3 in their opening match.
Additionally, Joe Salisbury and Neal Skupski moved forward as they overcame Germany-Russia’s Andreas Mies and Roman Safiullin with a score of 6-2, 6-4.
Conversely, Emily Appleton and her partner from Spain, Yvonne Cavalle-Reimers, fell short against Mexico’s Renata Zarazua and the Philippines' Alexandra Eala, losing 7-5, 6-4.