Stewart was hurt when his right knee jammed into the hard Marvel Stadium turf during the first quarter on Saturday night.
The 32-year-old limped off and headed to the changeroom for assessment as the Saints piled on six goals to one before quarter-time.
Stewart briefly returned after the first break with his knee strapped but was taken out of the game permanently before halftime.
St Kilda were up by as many as 40 points during the second term and led 10.5 (65) to 5.6 (36) at the main break.
Stewart was replaced by substitute Ted Clohesy, who had been called into Geelong's match-day squad when Smith was ruled out before the opening bounce with a calf injury.
Cats coach Chris Scott said boom recruit Smith had been "really close" to playing against St Kilda.
"As is our normal practice, we like to give them as long as possible," Scott said on Fox Footy before the game.
"There was a good chance that he was going to play, and we wanted to give him right up until game time really.
"It became clear in the last 24 hours that it was the most prudent thing to wait a little bit, but that gives us an indication that he'll be right next week."
Geelong take on the Brisbane Lions in a blockbuster clash at the Gabba in round three.
Smith's latest injury setback comes a week after his scintillating Cats debut, when he tore Fremantle apart in a 78-point win in round one.
The high-profile midfielder had also shone in pre-season and dominated against the Dockers with 32 disposals and one goal.
Smith missed the entire 2024 season with the Western Bulldogs because of a torn anterior cruciate ligament, before being granted his wish of a trade to Geelong.
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