He changed the Blaugrana's history that night, replacing Deco as a fresh-faced 17-year-old away to Espanyol in La Liga.
Fast forward 15 years and the Argentine has made 692 appearances for his club and scored 604 times.
Messi has helped his side to 34 trophies while winning five Ballon d'Ors for himself. Many fans regard him as the greatest player of all-time.
So, was his talent clear to see from the moment he stepped foot onto Espanyol's pitch? Was he always destined to become the best?
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Well, according to the defender who marked him that day, apparently not.
David Garcia had the honour of becoming the first-ever man to mark Messi - but it's fair to say the Argentine didn't impress his opponent very much during his short substitute appearance.
"It was normal [marking Messi that day], he was not what he is now, despite his innate talent," Garcia told Goal.
"Today he is confident and has grown a lot - nothing like what he was in that game. I don't remember anything special about marking him, it was like defending against any other player."
As well as suggesting that Messi was not memorable on his debut, the former Espanyol defender also said he's shocked at how much the Argentine has gone on to achieve.
"I sensed that he would be a very good player but not what he has become," the Spaniard continued.
"The truth is that at that time I did not think about what he was going to be.
"I thought that, like many boys from Espanyol or Barcelona, he was fulfilling the dream of debuting with his team being so young but on the pitch, you don't think about that."
Garcia might be the only defender in history to ever come off the pitch questioning Messi's talents. Hindsight is a wonderful thing.News Now - Sport News