Coach Tom Coughlin confirmed the injury on Sunday, saying that the Giants will "definitely miss" the 26-year-old Brown.
Brown suffered the injury during an interception return in Saturday's preseason game against the New York Jets. He fell to the turf untouched at the end of the return and immediately clutched his left knee.
"He made a lot of plays for us," Coughlin said Sunday. "So we'll definitely miss him."
Prayers go out to @StevieBrown27...both a great player and person...he will bounce back stronger than ever
— Henry Hynoski (@HenryHynoski) August 25, 2013
Prayers out to my dawg @StevieBrown27. We kno u gon bounce back ��
— Rueben Randle (@RuebenRandle) August 25, 2013
The Giants were already playing the Jets without starting safety Antrel Rolle, who is recovering from a sprained ankle. Rolle is expected to be ready for the season opener.
Brown had a team-leading eight interceptions last season and also had 307 return yards off the picks. Brown's breakthrough season led to the Giants signing the restricted free agent to a one-year deal to return as a starter.
Information from ESPN's Adam Schefter and ESPNNewYork.com's Ohm Youngmisuk and Kieran Darcy was used in this report.