Gonchar, one of the NHL's top offensive defensemen, has cartilage and ligament damage and had hoped to avoid surgery. He was hurt on a hit by Tampa Bay's David Koci in an exhibition game against the Lightning on Sept. 20.
Gonchar, 34, could be out until March, which would sideline him for most of the season.
"It is always difficult to lose a very talented player and leader for an extended period of time, but we all believe this is the best decision for Sergei," general manager Ray Shero said Tuesday in a statement.
Gonchar will have surgery in Pittsburgh. He did not accompany the team to Europe, where last season's Stanley Cup runners-up play an exhibition game Thursday in Helsinki against Finland's Jokerit team. The Penguins open the NHL season Saturday and Sunday against Ottawa in Sweden.
ESPN.com's Pierre LeBrun first reported that Gonchar would undergo surgery.
Gonchar had 12 goals and 53 assists last season for 65 points, second-most among defensemen. He tied a career-high with 67 points in 2006-07 (13 goals, 54 assists).
Gonchar has 37 goals and 153 assists in three seasons with the Penguins, after spending all or part of 11 seasons with the Washington Capitals and Boston Bruins. He is in the fourth season of a five-year, $25 million contract.
The Penguins also expect to be without their other top offensive defenseman, Ryan Whitney, until at least January. Whitney had surgery in August to correct a chronic bone problem in his left foot.
The injuries are a setback to a team that will begin the season without two of its top scorers from last season -- late-season pickup Marian Hossa, the third-leading scorer during the playoffs, and forward Ryan Malone. Hossa signed with Stanley Cup champion Detroit and Malone went to Tampa Bay.
Gonchar plays an important role on a developing team filled with young talent, including Sidney Crosby, Jordan Staal and Evgeni Malkin. Gonchar often serves as an interpreter for the Russian-speaking Malkin, who has lived with Gonchar and his wife.
Shero said the Penguins are confident Gonchar will "come back strong after this surgery. In the meantime, we'll look to our other defensemen to step up in his absence."
That means an expanded role for 21-year-old Kris Letang, who failed to make the team out of training camp last season but later had six goals and 11 assists in 63 games.
The injuries also may create ice time for 23-year-old Alex Goligoski, who was already being viewed as an option to replace Whitney before Gonchar was hurt. Goligoski had two assists in three games last season.
The loss of Whitney and Gonchar figures to thrust Brooks Orpik into more of a leadership role on the team, especially given the six-year, $22.5 million contract he signed in the offseason.
The Penguins also may rely heavily on defense-oriented defensemen Mark Eaton, returning from season-ending knee surgery in January; Hal Gill, obtained for draft picks from Toronto in February; and Darryl Sydor and Rob Scuderi.
Information from ESPN.com's Pierre LeBrun and The Associated Press was used in this report.