The Magpies confirmed Sidebottom suffered a medial collateral ligament injury in his right knee in an awkward tackle on Cameron Zurhaar in the opening 10 minutes at Marvel Stadium on Sunday.
Collingwood were clearly initially rattled by the Sidebottom injury but were able to keep a gutsy but scrappy North Melbourne at arm's length to claim a 16.9 (105) to 10.10 (70) win and maintain outright top spot.
The Magpies were celebrating Sidebottom's milestone and Mason Cox's 100th game but the occasion was soured when the wingman tackled Zurhaar then started feeling for his right knee, clearly in discomfort.
He headed straight down the race for assessment before being officially substituted out of the game and replaced by Will Hoskin-Elliott.
"He's done an MCL and will miss the rest of the game unfortunately," Collingwood football boss Graham Wright said in a statement posted to the Magpies' Twitter account.
Sunday's game was otherwise relatively routine for Collingwood against the struggling Kangaroos.
Jordan de Goey was at his dynamic best for the Pies, racking up 35 disposals, 10 inside-50s, 589 metres gained and one goal while Nick Daicos collected 32 disposals and had seven clearances.
Wingman Josh Daicos kicked three classy goals and Brody Mihocek had three, while Isaac Quaynor intercepted at will.
Former No.3 draft pick Will Phillips played arguably his best game for North Melbourne with 29 disposals and five clearances, while Nick Larkey finished with five goals.
The Magpies raced away with the first four majors of the game as the Kangaroos, lacking polish, struggled to go with the slick AFL leaders.
North kicked their first two goals of the game in the second quarter, while holding Collingwood to three for the term.
But the Magpies exploded after halftime, leaving the Kangaroos in their wake with a six-goals-to-two third quarter to nudge their lead out to 53 at the final change.
Kangaroos boom youngster Harry Sheezel went down to the rooms for treatment late in the third quarter after a boot to the face but returned.
Cox delighted the crowd in his milestone game when he took a towering mark over Ben McKay early in the final quarter, slotted his second goal and celebrated with aplomb.
The 17th-placed Kangaroos fought it out with a six-goal last quarter to keep the final margin somewhat respectable.
