The 6-foot-8, 210-pound Smith suffered the knee injury in practice earlier this week. Smith tore his left ACL last summer and missed his senior season at Las Vegas High School.
"Ray Smith is one of the most talented young players that has ever entered our program," Arizona coach Sean Miller said in a statement. "The news of his injury is incredibly disappointing on several levels. However, the togetherness of our program is one of our strengths. Our great fans, former and current players, our medical and coaching staffs along with Ray's family look forward to the challenges of helping him reach all of his goals and dreams.
"His journey in getting to the top of the mountain might be different, but I have tremendous belief that he will get there with this type of support, his amazing determination to succeed and the love of the game of basketball that he possesses. Today, Ray Smith remains one of the most talented young players we have ever had at Arizona and that has not changed."
Smith, who was ranked 29th in the Class of 2015 by ESPN.com, was expected to contend for a starting spot following the departure of Stanley Johnson and Rondae Hollis-Jefferson to the NBA. Smith already was on the radar of NBA executives because of his size and athleticism.
Teammate and fellow freshman Allonzo Trier tweeted support for Smith on Friday night.
Anderson, who sat out last season, is considered more of a power forward while Tollefsen is expected to play both forward spots. Another option for Wildcats coach Sean Miller could be to go with a smaller lineup, teaming the 6-foot-5 Trier with two smaller guards such as 5-foot-11 point guard Parker Jackson-Cartwright and 6-foot-3 guard Gabe York.