The midfielder, who missed the second half of last season with a damaged cruciate ligament, went off early in their defeat against Aston Villa last weekend.
Bentancur was on the receiving end of a strong challenge from Matty Cash and had to be withdrawn after 32 minutes.
Matters were made even worse for Spurs at full-time as they fell to their third defeat in a row as Villa won 2-1 in north London.
There has not been any official confirmation on the extent of the Uruguayan's injury but it's set to be a while until he returns.
He will be the latest addition on Spurs' long list of absentees that currently includes James Maddison and Micky van de Ven.
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Bentancur had made his first start for the club since February when Villa made the visit to the Tottenham Hotspur Stadium.
His previous three appearances this season had come off the bench but fans may have to wait until 2024 for his return to action.
The 26-year-old would certainly have had a strong case to be named in their starting XI for the upcoming busy festive period.
However, boss Ange Postecoglou may have to tweak his plans even further as he deals with the club's latest injury.
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Pierre-Emile Hojbjerg came on in his place and lined up with Giovani Lo Celso in the midfield for the rest of the match.
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It didn't prove to be enough though as Spurs lost a consecutive match in the Premier League have previously been unbeaten.
Lo Celso opened the scoring but Villa hit back on the stroke of half-time via a Pau Torres header.
Ollie Watkins' strike just after the hour mark was enough for Unai Emery's side to take all three points back to Villa Park.