The Rangers begin a long stretch without their top scorer and captain when they face the Colorado Avalanche at Madison Square Garden on Monday night.
New York (1-1-1) has dropped consecutive games after a season-opening 6-3 win at Buffalo on Oct. 9.
Brian Boyle forced overtime by scoring twice in the third period Friday, but the Rangers fell 4-3 to Toronto in their home opener.
New York was dealt an even greater blow with Gaborik and Drury leaving the defeat with injuries.
Gaborik, the team leader with 42 goals and 44 assists last season, is out at least two weeks after suffering a separated shoulder when he was slammed into the glass by the Maple Leafs' Colby Armstrong, who was assessed a boarding penalty.
"If he is going to be out for any extended period of time, that just means the other 22 guys are going to have to step up," said center Brandon Dubinsky, who is tied with rookie Derek Stepan with a team-high three goals. "I don't think anyone else is going to step up and score 40 goals, but we just have to pick up the slack and find ways to get wins."
Drury, who missed the first two games of the season with a broken left index finger, broke the finger again -- in a different place -- and will be lost for six weeks. The center was replacing Erik Christensen, who is expected back Monday after missing a game with a leg injury.
Adding to the misery, Vinny Prospal will undergo knee surgery Tuesday and is out indefinitely. The left wing's 58 points last season were second on the team.
"It's too bad for them, and it's too bad for us, obviously," Boyle told the team's official website.
Gaborik, Prospal and Drury combined for 76 of New York's 219 goals last season.
The injuries to the Rangers' top offensive threats will put added pressure on Henrik Lundqvist, who has a 3.95 goals-against average in three games.
He's 1-0-1 with a 2.47 GAA in two games against the Avalanche (3-2-0), but didn't face them in the Rangers' 3-1 victory in the lone meeting last season Jan. 31.
Gaborik had a hat trick and Prospal added two assists in that matchup at Colorado.
The Rangers beat the Avalanche 6-1 in the last meeting at MSG on Feb. 28, 2009.
Colorado is trying to conclude a five-game road trip over .500 after falling 5-2 to the New York Islanders on Saturday.
"We tried to get too offensive, and when you start to get fancy, that's when you get into trouble," said T.J. Galiardi, who has two goals and one assist in the last two games.
Craig Anderson may be in net for a third consecutive game as he tries to rebound from his worst performance of the season. He allowed four goals on 24 shots Saturday, a night after outplaying Martin Brodeur with a 41-save performance in a 3-2 win over New Jersey.
Anderson is 2-1-1 with a 1.72 GAA and a shutout in four games against the Rangers, winning his two contests at MSG while allowing one goal on 78 shots.