The 35-year-old turned home Nuno Mendes's deflected cross after just 12 minutes to give PSG the lead at the Parc des Princes, bringing up a remarkable milestone in the process.
The goal was the 701st of Messi's club career, while he also boasts a record 299 assists throughout his time in senior club football too, taking him to 1,000 goal involvements overall.
Assist statistics have only become fully reliable relatively recently, while the likes of Pele and Romario claim to have scored more than 1,000 goals in their careers, although those figures are understood to include friendlies and youth games too.
Messi is therefore thought to be the first player in modern football to reach the 1,000 goal involvement landmark at the top level of the game.
The Argentine's great career rival Cristiano Ronaldo is currently on 912 combined goals and assists in his career, despite playing significantly more matches than Messi.
The World Cup winner has scored 18 goals and created 16 more in 29 appearances for PSG across all competitions this season, including 13 goals and 12 assists in the league.
Messi's latest strike was the 799th goal of his career overall, with 98 international strikes to add to his 701 at club level, meaning that he is just one away from another milestone of 800 career goals.
The goal against Nantes ultimately helped PSG pick up a third consecutive league win, despite Nantes fighting back from 2-0 down to level things at 2-2.
Kylian Mbappe capped off the eventual 4-2 victory with his 201st goal for PSG, surpassing Edinson Cavani as the club's all-time leading scorer at the age of just 24.
The victory and milestone capped off a memorable week for Messi, who was named The Best Men's Player of the Year by FIFA on Monday after inspiring Argentina to World Cup glory in 2022.