The Mavericks announced that Nowitzki, 34, is expected to resume on-court activities within approximately six weeks, which means he will miss the beginning of the regular season.
The Mavs have 13 regular-season games scheduled during that six-week window.
"We've got to really buckle down," Dallas coach Rick Carlisle said. "Six weeks is a long time. A week and a half of it is non-season time, so that's a bit of a plus, but NBA games are hard and we're going to have to have everybody ready to play. Simple as that."
Nowitzki, an 11-time All-Star, has missed the Mavericks' last three preseason games due to swelling and soreness in the knee. He hoped to put off the surgery until after the season, but it was determined that he needed to have the cause of the inflammation dealt with now.
The Mavericks' medical staff drained the knee twice this month, and the swelling returned within days both times. Nowitzki's knee did not respond as hoped to a program of rest, icing and low-impact conditioning work this week, leading to the decision to get the knee scoped.
"If it's going to keep swelling up on me, that's obviously not a way to go throughout an 82-game season and hopefully long playoff run," Nowitzki said Monday after the swelling returned following his participation in three consecutive practices.
The knee started bothering Nowitzki, a 14-year veteran, during last season's training camp. He struggled mightily at the beginning of the lockout-compressed season, leading to his taking four games off to focus on conditioning. The knee wasn't an issue for the rest of the season, but Nowitzki had his worst statistical year since his second season in the NBA, averaging 21.6 points and 6.8 rebounds for a defending championship team that was swept in the first round.
Nowitzki wrote on his Twitter account Saturday, "Thanks for all the kind words and thoughts and prayers. Means a lot to me. I hope to be back out there pretty soon. Will keep u posted."
The Mavs open the season on the road Oct. 30 against the Los Angeles Lakers, and six of their next eight opponents were lottery teams last season.
"It's never going to be easy to lose a game-changer for six weeks," Carlisle said. "We know that, but we're going to have to make up for it in other areas. We're going to have to play with grit and guts, and we're going to have to raise our level of efficiency in all areas."
The biggest concern about Nowitzki missing time might be the stunted development of the remodeled Mavs' on-court chemistry. There are eight newcomers on the roster, including starting point guard Darren Collison, shooting guard O.J. Mayo and center Chris Kaman.
Kaman, meanwhile, has a strained calf and will not make the trip for the Mavs' preseason game against the Atlanta Hawks on Saturday. Carlisle said Mavs athletic trainer Casey Smith will stay in Dallas this weekend to monitor Kaman and Nowitzki. The Mavs hope Kaman will be able to return next week.