Full-back Brown, who has won 72 caps for England and made more than 300 appearances for Harlequins, is expected to be out for between "six to nine months".
The 34-year-old was left out of England's squad for the Rugby World Cup as Eddie Jones' side made it to the final in Japan, where it was defeated by South Africa.
"Losing Mike is a big loss. He's tried hard to train and play over the past few weeks," Harlequins' head of rugby Paul Gustard said.
"Unfortunately his situation worsened, and it would be damaging to his long-term knee health to try and play."
Brown has played five times for Harlequins this term, having initially sustained the knee issue in pre-season.