Messi netted his side's second goal in the 3-0 win in Athens as Barca not only secured their place in the last 16 of the competition but also ensured they would be going through to the knockout stages as group winners.
Messi's strike means he has scored 23 times in all competitions for Barca already this season - 16 in his last 11 appearances - and extended his club-record tally in the Champions League to 31 goals in 49 matches.
It was also the 150th goal the 23-year-old reigning FIFA World Player of the Year has scored in official matches for Barca.
Mascherano said: "We have to enjoy Messi because it will be many years before we see a player of this magnitude again. He will go down in history.
"We hope to win the Clasico because it's important, but they are still only three points and we don't have to go mad about it. We must try to go into the game with calm."