Toronto put the veteran receiver on the six-game injured list Friday. Durie, 33, broke his right clavicle again Wednesday after diving for a pass during practice.
Durie first broke it during Toronto's 48-15 home win over Saskatchewan on July 5. He underwent surgery and missed seven games before returning Sept. 13 and playing in two contests.
Toronto head coach Scott Milanovich said the two injuries are similar and Durie will likely require surgery again.
"It's not exactly the same break," Milanovich said. "Part of it held up, part of it didn't. That's how I understand it.
"I'm anticipating he's done for the season but that isn't set in stone."
Rookie Robert Gill will replace Durie on Saturday when Toronto (4-8) hosts Edmonton (9-4) in the first of four straight home games at Rogers Centre. The Argos are currently third in the East Division, two points behind Hamilton and Montreal while the Eskimos are tied with Saskatchewan for second in the West.
"Robert Gill has as much juice as anybody in this league and we'll find somebody to do some of the other dirty work that Andre does," Milanovich said. "Now, can one guy do the job Andre did? Probably not.
"But I do think we're in a much better place than we were four, five weeks ago when we had all the injuries."
Toronto also released former starting linebacker Shane Horton on Friday.
The five-foot-10 199-pound Durie had career highs in catches (92) and receiving yards (986) last season. The Mississauga, Ont., native is also a versatile performer as he can play running back — his former position at York — and contribute on special teams.
Durie has been limited to just 19 catches for 214 yards and a TD this season.
"We're definitely going to miss his production ... and his leadership as well," Toronto quarterback Ricky Ray said. "We've just got to try and fill that void and make some plays in his absence."
Cornerback Pat Watkins, who spent two seasons with Toronto before signing with Edmonton this off-season as a free agent, said losing Durie is big for the Argos but it's Ray who makes their offence go. Despite an abundance of injuries to Argos receivers, Ray leads the CFL in pass percentage (68.2 per cent) and TDs (22) and is second in passing yards (3,206).
"He (Ray) is going to be on his 'A' game, we know that," Watkins said. "Ricky Ray has always been sharp. I haven't really seen him off his game too many times.
"We expect him to go out and play like Ricky Ray so we're going to play like we can play."
Ray spent his first nine CFL seasons with the Eskimos and led them to two Grey Cups before being dealt to Toronto in December 2011. Ray guided the Argos to the 2012 Grey Cup but is just 1-3 against his former team, including a 41-27 road loss in Edmonton on Aug. 23 where Ray was sacked five times and threw three interceptions.
He'll face an Edmonton defence that was sensational in last weekend's 24-0 win over Saskatchewan, the Riders' first shutout loss since 1986. But the Eskimos will be minus defensive linemen Eddie Steele and Gregory Alexandre — both Canadians — and Marcus Howard.
Veteran Almondo Sewell and rookie Cedric McKinley will replace Alexandre and Steele at tackle while Canadian Bo Adebayo, plucked recently from Montreal's practice roster, was added to the 46-man roster.
"They understand what needs to be done (Saturday)," Watkins said. "I'm pretty sure after seeing them this week in practice they have a full understanding of how the game is played.
"We're going to be there to support them."
Edmonton head coach Chris Jones also figures into the equation. A defensive guru, Jones is often unconventional in his defensive schemes, which makes it difficult for opposing offensive coaches to know exactly how to gameplan against him.
Milanovich knows this firsthand. He and Jones are close friends and one of Milanovich's first moves after being named Argos head coach was to hire Jones as his defensive co-ordinator.
Toronto hasn't played since its 40-23 road win over B.C. on Sept. 19 but Milanovich said time isn't an advantage when preparing to face Jones's defence.
"'The thing with him is you don't know what he's going to do," Milanovich said. "So it really doesn't matter if you have a long week or short week because he could completely change everything the first play of the game and throughout the entire game.
"We understand what's ahead of us. He's as good as it gets on defence and our offence is going to have a great challenge."
Jones is also a free spirit. He rides motorcycles, dresses in all black on the sidelines and has drawn the ire from other coaches for not shaking hands after games.
But Milanovich says, that's Chris Jones.
"I should go all black, it's slimming," Milanovich said with a chuckle. "He was upset we didn't have all black when he was here ... but that's the way he's been since I've known him."
And so Milanovich won't go looking for a pre-game handshake Saturday.
"I've had enough handshakes," he said with a smile. "We'll be all right."