Barcelona were reduced to 10 men in just the 10th minute of the contest, as Eric Garcia was handed a red card for bringing Takumi Minamino to the ground after a poor pass from the away side's goalkeeper Marc-Andre ter Stegen had put his team in trouble.
Monaco needed just six minutes to take advantage, with Maghnes Akliouche collecting the ball down the right before dancing into the Barcelona box and picking out the bottom corner with a brilliant low strike.
The Catalan team were wobbling, but with their first effort, they levelled, and it came from Lamine Yamal, who found the bottom corner from just outside the penalty box to register his first Champions League goal, becoming the competition's second-youngest goalscorer in the process behind teammate Ansu Fati.
Fati, who was back in the Barcelona squad on Thursday, was 17 years and 40 days old when he first registered in the competition, while Yamal netted at the age of 17 years and 68 days old.
Monaco, though, were back ahead in the 71st minute when 18-year-old George Ilenikhena raced clear and finished into the back of the net on his debut appearance in the competition.
Barcelona were unable to respond for a second time in the European affair, as Hansi Flick's team were beaten for the first time during the 2024-25 campaign.
MONACO VS. BARCELONA HIGHLIGHTS
Eric Garcia red card vs. Monaco (10th min)
Barcelona are reduced to 10 men in the 10th min of the contest, as Garcia is given his marching orders for bringing Minamino to the ground when the forward was bursting into the box.
A poor pass from Ter Stegen put the Spaniard in trouble, and Garcia brought Minamino down, leading to the 23-year-old being given his marching orders in the European affair.
Maghnes Akliouche goal vs. Barcelona (16th min, Monaco 1-0 Barcelona)
Monaco make the most of their one-man advantage, as Akliouche finds the bottom corner with a brilliant strike after dancing his way into the Barcelona penalty box.
Lamine Yamal goal vs. Monaco (28th min, Monaco 1-1 Barcelona)
Barcelona, out of nowhere, level the scores in the 28th minute of the contest, and it is a first-ever Champions League goal for the brilliant teenager Yamal.
The forward finds space just outside the Monaco box before firing the ball into the bottom corner.
George Ilenikhena goal vs. Barcelona (71st min, Monaco 2-1 Barcelona)
Monaco are back in the lead against Barcelona, and it is a landmark moment for 18-year-old Ilenikhena, who races clear before firing into the back of the net on his Champions League debut.
MAN OF THE MATCH - VANDERSON
Barcelona are believed to have been scouting Vanderson during Thursday's affair, and they would certainly have been impressed with what they saw from the Brazilian.
Indeed, Vanderson is thought to be a transfer target for the Catalan outfit, and he provided two assists during an excellent all-round performance in the Champions League clash.
As well as his assists, the right-back won two aerial duels, while he finished with 31 accurate passes.
MONACO VS. BARCELONA MATCH STATS
Possession: Monaco 52%-48% Barcelona
Shots: Monaco 15-4 Barcelona
Shots on target: Monaco 8-1 Barcelona
Corners: Monaco 10-0 Barcelona
Fouls: Monaco 14-14 Barcelona
BEST STATS
WHAT NEXT?
Barcelona will be aiming to make it six straight wins at the start of the new La Liga campaign when they head to Villarreal on Sunday evening, with their next European game not until October 1 against Young Boys.
Monaco, meanwhile, will take on Le Havre in Ligue 1 on Sunday afternoon, and Les Monegasques will then resume their Champions League campaign away to Dinamo Zagreb on October 2.