Antonio Conte's side traveled to the King Power Stadium hoping to maintain their positive push following last weekend's big win over Man City.
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Rodrigo Bentancur opened the scoring for Spurs, but they were pegged back soon after.
Mendy scored a brilliant goal, as the ball fell to him following a corner clearance and he slammed it into the top corner from the edge of the box.
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Scores were level for just two minutes as Leicester won the ball high up the pitch and quickly took the lead.
Kelechi Iheanacho set up James Maddison for a simple finish past Fraser Forster.
Maddison's excellent display came after Tottenham assistant Christian Stellini's comments, suggesting his club were tracking his progress under the tutelage of Brendan Rodgers.
Prior to the match, Stellini said: "We like Maddison as a player. He is an important player in this league."
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"A player with an important type of skill, like his delivery, his cross. His right foot is a very important foot so he shoots, he crosses, he takes the set-pieces.
"He is a player you have to take care of. When you play against this player, you have to be careful.
"When you feel how important this type of skill is, for sure you like this type of player. He's a player with talent.
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"At the moment he's playing for Leicester, a team we play against. We take care of him like an opponent."
Before half-time, Iheanacho made it 3-1 following some further careless Tottenham defending.
It was an alarming turnaround for Tottenham having been riding high just six days prior.
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Late in the second half, Harvey Barnes added Leicester's fourth from outside the box after receiving Maddison's pass to secure a big win for Rodgers' side as they picked up a huge boost in their fight against relegation.
For Tottenham and Conte, this was a big blow as Man United and Newcastle will now have the chance to pull away from them in the race to secure Champions League football.