The Argentine is just one goal behind Telmo Zarra’s 59-year-old record of scoring 251 goals for Athletic Bilbao.
However, his Madrid rival Cristiano Ronaldo has also started the season in record-breaking fashion.
Here, AFP Sports looks at the numbers behind the rivalry between the two best players in the world:
– Messi highest scorer in Clasicos
Messi already knows the feeling of breaking a significant record at the Bernabeu. On his last visit he passed compatriot and Madrid legend Alfredo di Stefano by scoring a hat-trick to become the leading goalscorer in El Clasicos with 21 in 28 matches.
Ronaldo is down in seventh on that list with 13 in 21 games against Barca since he joined Madrid in 2009.
– Ronaldo averaging over two goals a game in La Liga
Ronaldo’s incredible run of scoring 15 goals so far this season in La Liga is an all-time record after eight games.
Even more amazingly, Ronaldo has only taken seven appearances to reach that mark having missed Real’s defeat to Real Sociedad due to injury.
By contrast, Messi’s record of seven goals in eight games seems humble, however, he has also provided a league high nine assists.
– Both men on the verge of Champions League history
Messi and Ronaldo were both on target as Barca and Madrid continued their march towards the Champions League last 16 with victories over Ajax and Liverpool respectively.
Both are now on the verge of surpassing Real legend Raul’s record of 71 Champions League goals with Ronaldo on 70 and Messi just one further back.
– Ronaldo the hat-trick king
One of the few feats so far beyond Ronaldo in his Madrid career has been a hat-trick against Los Blancos’ eternal rivals.
The Portuguese bagged three hat-tricks in four league games this season move level with Zarra and Di Stefano on 22 in La Liga.
Messi has 19, but two of those came against Madrid in a 4-3 win last season and a 3-3 draw in 2007.
– Ballon d’Or decider?
With the vote for Germany’s World Cup winners likely to be split amongst a number of players, Messi and Ronaldo are the favourites once more and Saturday’s spectacle provides the ideal stage to make a late case to voters.