The Polish star striker scored the leading goal in the 10th minute after he himself was brought down by Brest goalkeeper Marco Bizot.
The only two who have reached three figures in Champions League scoring before him are Cristiano Ronaldo and Lionel Messi. They scored 140 and 129 goals respectively in the tournament.
Dani Olmo doubled the lead midway through the second half, and in overtime Lewandowski set off on the next 100 when he sealed the result with an assist from substitute Alejandro Balde.
The 3-0 victory lifted Barcelona to 2nd place in the Champions League table before the last nine games of the round are played on Wednesday. Only Inter are ahead, after their 1-0 win over Antonio Nusa and his RB Leipzig.
Lowered by self-interest
An own goal by Castello Lukeba from a Federico Dimarco free kick in the 27th minute was the only score of the evening in Milan. Nusa played the whole match, but never managed to break through the home defence.
Inter have not yet conceded a goal in the Champions League this autumn and are 7-0 after five games. The team tops the table with 13 points before Liverpool, who are the only team without a point loss, play on Wednesday against a Real Madrid in need of points.
RB Leipzig have lost all five of their games, and their hopes of promotion are about to disappear.
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Atalanta ravaged
Atalanta is one of four teams still unbeaten in Champions League league play, and the team is up to fourth place after a 6-1 win over Young Boys in Switzerland. Mateo Regetui and Charles De Ketelaere scored twice each.
German league champions Leverkusen are also flying high, crushing Salzburg 5-0 with two goals from Florian Wirtz. Leverkusen is fifth in the table with the best goal difference of five teams on ten points.
Bayern Munich beat Paris Saint-Germain 1-0 with Kim Min-jae scoring and are up to nine points, while PSG are struggling with just four points from five games.
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