The game -- set for Jan. 1 in the stadium in Ann Arbor, Mich. -- was scratched, the NHL said in a release, because due to the lockout "the League was not in a position to do all that is necessary to adequately stages events of this magnitude."
The Toronto Maple Leafs and Detroit Red Wings were to have played the game before an expected crowd of 120,000.
The NHL also said the Hockey Winter Festival, a series of events in Detroit beginning Dec. 15, was canceled.
The league said Toronto and Detroit would be scheduled for the next Winter Classic and that it would be played in Michigan Stadium.
Among the preparations for the game and festival was the construction of outdoor hockey rinks both at Michigan Stadium and Detroit's Comerica Park, home of baseball's Detroit Tigers.
"The logistical demands for staging events of this magnitude made today's decision unavoidable. We simply are out of time," said NHL Deputy Commissioner Bill Daly in a release. "We are extremely disappointed, for our fans and for all those affected, to have to cancel the Winter Classic and Hockeytown Winter Festival events."
The league has canceled its regular-season schedule through the end of this month while owners and the players' union try to work out a new labor deal. The two sides haven't formally met since Oct. 18.
The league locked players out Sept. 15 in a dispute centered mainly on allocation of hockey-related revenues. The league is looking to reduce the players' share of those funds, which the most recent collective bargaining agreement set at 57 percent.
The owners also seek to do away with salary arbitration and want to alter free-agency rules.