Mahrez struck with a 39th minute penalty to score for the seventh successive game after Raheem Sterling had been brought down to send Pep Guardiola’s side in at the break holding the advantage.
And De Bruyne then sealed the deal with fine 69th minute effort from another Bees error to secure our 19th league win of the season and move us 12 points clear at the top of the table.
Game of patience
Just as in December’s clash in the capital, the Bees proved obdurate opponents and made City work hard to find space and openings in a cagey first 30 minutes.
Gradually however, the champions and league leaders began to impose ourselves on proceedings.
We served a first notice of intent on the half hour.
Mahrez was the architect, teasing in a low curling cross into the six-yard box with Bees keeper David Raya just deflecting the ball away from the on rushing Raheem Sterling before Joao Cancelo fired the follow-up over the bar.
Another patient move then saw Sterling spectacularly fire a diving volley narrowly over as latched onto an exquisite Foden delivery into the box from Stones’ instant lay-off.
City were knocking on the door and it was Aymeric Laporte’s turn to go close on 36 minutes. The central defender was found in space 10 yards from Dias’ neat header but sent his left foot shot just inches wide of the target.
The breakthrough finally arrived on 39 minutes from man of the moment Mahrez who expertly converted from the penalty spot.
A Brentford mix-up at the back saw Sterling seize possession and drive into the box only to be brought down by Mads Roerslev.
Referee Darren England instantly pointed to the spot and Mahrez needed no second invitation to slot home the spot kick as he found the target for the seventh straight game and took his tally for the season to 16.
However, City then had a major scare just before the break after an unlucky Stones slip saw Rico Henry find space on the left edge of the box.
Having exchanged passes with Ghoddos, he whipped in an inviting ball into the heart of the box for the onrushing Sergi Canos but Ederson came out bravely to avert the danger, taking a blow to his neck for his troubles.
Striving for the all-important second goal Cancelo demonstrated some nifty footwork on 54 minutes waltzing past three defenders only to fire straight at Bees keeper Raya.
Brentford remained a threat on the break though and City were relieved to see Frank Onyeka’s 60th minute flick shot gathered by Ederson after and a fine move from the visitors.
But City would not be denied and the crucial second did arrive on 69 minutes via De Bruyne – and it was from another Brentford error.
Raya’s attempted pass out was intercepted by Sterling on the edge of the box but the Bees keeper partially redeemed himself by blocking the shot.
However, De Bruyne pounced on the follow up superbly drilling home from 18 yards to double City’s advantage.
Raya then produced a fine effort to tip away Cancelo's low drove as City sought to extend our advantage.
But though we couldn't add a third, it was job done and another vital three points in the account.
Man on the spot
Up until this season penalties had occasionally caused a touch of consternation for City over the past year or so - but in Riyad Mahrez we have found a man with the coolness and composure to shoulder the big responsibility.
Another successful conversion from 12 yards made it six penalties out of six for the Algerian this season and it was the seventh straight game where he has found the target.
In the wake of his brace against Fulham at the weekend, which included another nerveless penalty, Pep Guardiola was quick to praise Mahrez’s ability from the spot.
“In the last year we struggled with penalties and now he is a guarantee. He has the personality to take the ball and do it,” the manager declared.
And the 30-year-old further amplified those words with his latest penalty poise further illustrating that he is arguably in the best form of his City career.
A deadly finish from 12 yards again demonstrated that he is also proving to be City’s man on the spot whatever the circumstances!
Man of the match
Joao Cancelo produced another excellent all-round display.
Deployed at left-back once again, the Portuguese international was both assured in defence and a potent attacking threat.
And only a fine save from Brentford keeper Raya prevented him rounding off another fine night's work with a goal.
A class act all round.
Pep Guardiola’s verdict
"This was an important victory, three more points to reach 60 with 14 games left, next up Norwich.
"Riyad Mahrez was especially good and so solid in the penalty, which we struggled with in previous seasons. It was difficult for the wingers as they did not have space, but we won.
"Joao Cancelo was the best winger we had, he was better than our [traditional] wingers. He was really good, him and John Stones were so important today to create more space for the other guys with their movement."
CITY: Ederson, Stones, Dias, Laporte, Cancelo, Rodrigo, De Bruyne, Bernardo, Sterling, Foden (Gundogan 70), Mahrez (Grealish 65)
Subs: Steffen, Walker, Ake, Zinchenko, Fernandinho, Delap, McAtee
BRENTFORD: Raya, Henry, Pinnock, Jansson, Ajer, Roerslev, Norgaard, Onyeka, Jensem, Ghoddos (Mbeuno 62), Canos (Dasilva 62)
Subs: Fernandez, Lossl, Wissa, Baptiste, Sorensen, Stevens
What it means
A 19th Premier League win of the season saw City extend our lead at the top of the table to 12 points from second-placed Liverpool.
The Anfield side do have two games in hand and play the first of those tomorrow night when they entertain Leicester.
But with the business end of the season fast motoring into view, points on the board are the priceless commodity right now.
It’s City in the driving seat with our rivals knowing they can ill afford any slip-ups.
City are back in Premier League action on Saturday when we make the long journey to Norwich City.
Kick-off at Carrow Road is 5.30pm, with Guardiola’s side seeking a league double over the Canaries in the wake of our 5-0 win here way back last August.
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