Crabtree required surgery on a torn Achilles tendon in his right leg back in May and has missed every game of the season so far.
Last season, Crabtree posted career highs of receiving 1,105 yards off of 85 catches, scoring nine touchdowns, so his return to action this weekend will serve as a major boost to a team battling to reach the playoffs.
He told the club's official website: "I'm really ready to play. It's been a long time coming. I just want to go out there and play football and it's going to be good to be out there again.
"Everything happens for a reason and now I feel comfortable. I'll felt good in practice and had fun.
"Whilst I've been out I've still been around the game, learning every day from the sidelines. I've learnt from watching Anquan Boldin so I'd bee a fool not to steal something from him."
The 49ers are battling with the Cardinals to reach the playoffs from the NFC West, with the Seattle Seahawks looking likely to be the division's top seed.
Crabtree's return will be against divisional rivals the St Louis Rams on Sunday.