The 49ers placed Malcolm Smith on injured reserve, the team announced on Monday.
To replace Smith, San Francisco signed linebacker Austin Calitro to a two-year deal.
During practice on Saturday, Smith sustained a torn right pectoral muscle.
He signed a 5-year, $26.5 million deal during the offseason, with $11.5 million in guarantees.
Calitro -- who played his college ball at Villanova -- originally signed with the Jets as an undrafted rookie free agent on May 5. He was waived on May 15.
At Villanova, he appeared in 48 games and registered 220 tackles, 26 tackles for loss, 8.5 sacks, eight passes defensed, three forced fumbles and two interceptions.
As a senior in 2016, Calitro tied the team lead with 86 tackles and also registered 12 tackles for loss and 3.5 sacks, earning First-Team All-CAA honors.
In 2015, he led the team in tackles (90) and forced fumbles (three), finished with 11.5 tackles for loss and 4.5 sacks while earning Third-Team All-CAA honors.
He played in all 14 games in 2014 and had 33 tackles, 2.5 tackles for loss, one interception and one pass defensed.
Following a redshirt season in 2012, he appeared in 10 games and had 11 tackles in 2013.
San Francisco 49ers media services contributed to this story