Mane had already scored his first official goal for the German giants during last week's German Super Cup win over RB Leipzig, and now he has chalked his first one up in the Bundesliga.
The 30-year-old forward glanced home a Serge Gnabry cross to make it 3-0 as Bayern crushed last year's Europa League winners.
Joshua Kimmich's started the rout with a free-kick in the fifth minute, with Benjamin Pavard making it two five minutes later.
Jamal Musiala (35) and Gnarby (43) took the score to 5-0 by half-time, with Musiala adding Bayern's sixth seven minutes from time. Mane claiming the assist on the final goal.
Randal Kolo Muani got one back for Frankfurt in the 64th minute, but it was merely a consolation.
Die Adler will have to pull their socks up if they want to get anything out of the UEFA Super Cup next Wednesday when they face Champions League winners Real Madrid.
The Senegalese star was one of five different goal scorers for Munich, immediately making up for the loss of Robert Lewandowski by joining Joshua Kimmich, Benjamin Pavard, Jamal Musiala (two) and Serge Gnabry in getting on the scoresheet.
"The four up front, they had fun," said Nagelsmann after the match.
Frankfurt coach Oliver Glasner could do little but acknowledge his opponents' superiority.
"The whole time, the boys tried everything, but Bayern were just two good for us. Today we didn't have a chance," said the coach.
As for Nagelsmann, he admits that after 10 straight Bundesliga titles, winning the league has begun to feel like normality for his side.
"When you win ten in a row, yes it starts to feel normal," he told broadcaster DAZN.
"But I don't really care if it feels normal or not - but yes, it can stay 'normal'.
"The first half was outstanding. I don't think it'll always be like this, but we should be satisfied."