Márquez is the latest rider to finalise a contract for 2021 and beyond, with several top MotoGP deals coming to an end this year.
Yamaha has already confirmed Fabio Quartararo and Maverick Viñales for its factory team in 2021, leaving out Valentino Rossi, who was not ready to commit for a further season.
Márquez’s new team-mate – his brother Alex – has a single year deal for his debut season in MotoGP.
“We are happy to announce that, after the end of the current season, Marc will stay in the Honda family for four more years,” said Yoshishige Nomura, president of HRC.
“We started talking a few months ago, as both parties wanted to stay together and continue winning. Marc started his career in the premier class in 2013 and with him we have won six of the last seven MotoGP titles.
“As a unique champion, he deserves a unique deal. I am very confident in this partnership and I wish everyone involved continued success.”