The home side had plenty of chances to take the lead in the first half before Raheem Sterling was fouled in the box by Mads Roerslev. Mahrez then dispatched the spot kick into the top-left corner.
After giving up possession, Brentford keeper David Raya could only parry Sterling’s shot into the path of De Bruyne, who sealed the victory in the 69th minute.
Norwich got off to a good start in their clash with Crystal Palace with Finn Teemu Pukki opening the scoring just 38 seconds in after being teed up by Adam Idah.
Palace found the equaliser in the 60th minute through Wilfried Zaha, who cut in from the left before unleashing a brilliant strike into the far corner.
Zaha had a chance to win it from the penalty spot soon after but slipped as he made contact with the ball, dragging his effort wide in the process.
From magic to misery for Wilfred Zaha ????
Goal of the season contender to potentially the worst penalty you'll see in the span of three minutes.
Over in north London, Spurs went down to Southampton after conceding two late goals.
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Che Adams broke the 2-2 deadlock in the 82nd minute with a cool header from a delightful ball in from captain James Ward-Prowse, which was nearly identical to his assist for Mohamed Elyounoussi just a few minutes earlier.
It could end up a costly loss for Spurs who are locked in a battle with a few other clubs for the last Champions League spot.
Aston Villa and Leeds played out a frenetic 3-3 draw in Birmingham with the six goals coming in a 54-minute block.
New recruit Philippe Coutinho, on loan from Barcelona, opened the scoring for the Villains before laying on two assists for Jacob Ramsey.
Daniel James, playing in the unfamiliar No.9 role for the visitors, was rewarded for his hard work with two goals.
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Diego Llorente equalised for Leeds in the 63rd minute after Tyrone Mings failed to clear his lines following a corner situation.
More Premier League action to come tomorrow morning, with Leicester travelling to Anfield to take on Jurgen Klopp’s side and Wolves hosting Arsenal. Kick-off for both clashes is set for 6:45am (AEDT).