Pep Guardiola's side profited from first-half goals from Gabriel Jesus and Ilkay Gundogan, before Raheem Sterling netted in the second period to put the game to bed after Christian Eriksen had given Spurs a slight lifeline.
Victory for the Citizens now leaves Guardiola just three points away from earning his first ever Premier League title and City's third, while defeat for Spurs ends a 14-game unbeaten run in the league for Mauricio Pochettino's charges.
The visitors were lightning quick on the counter and profited from a high Tottenham line, this time as David Silva drove through the middle before shifting wide to Kevin De Bruyne, the playmaker firing wide from range.
Tottenham were unable to keep up with the away side's movement, but Davinson Sanchez also did himself no favours when he lost track of Jesus for the opening goal, allowing the striker to beat the offside trap, latch on to Vincent Kompany's long ball forward and finish under the body of Lloris.
Spurs failed to respond to that mistake by showing more defensive frailty moments later as Sterling was left to break beyond the defence, where he was then brought down under a sliding challenge from onrushing keeper Lloris.
The challenge looked to have been outside of the box, but referee Jon Moss pointed to the spot for a City penalty. The decision allowed Gundogan to step up and send Lloris diving the wrong way, pushing City into a 2-0 lead in the 25th minute.
Pochettino's men were uncharacteristically poor in the first 45 minutes as both Eric Dier and Mousa Dembele were left overrun in midfield. City's possessional dominance soon allowed Silva to try to add a third from the edge of the area, although Lloris leapt across to save with both hands.
Somehow, with very little indication, the hosts were able to find a route back into the game just before half time, despite City's total control of the first period. Harry Kane finally came alive to play in Eriksen beyond the last man and he profited from a fortunate deflection to pull things back to 2-1.
Spurs were much improved after the break and they started to ask a few more questions, although the half's first major chance fell to Jesus, as he again broke off Sanchez only to skew wide when faced with testing Lloris.
Echoes of last weekend's defeat to Manchester United might just have spurred City forward as they went in search of a third. After some more standout build-up play, the visitors came up short again when Silva's cut-back saw Sterling's shot blocked on its way to goal.
Much had been made of Sterling's profligacy before the game, although the winger finally netted to put City in the driving seat after 72 minutes, the England international smashing home from close range after Lloris had originally saved a shot from Jesus.
In the end the game was never beyond City as Guardiola's men returned to winning ways with a commanding display both in possession and on the break, leaving the Sky Blues within touching distance of Premier League glory.
TOTTENHAM HOTSPUR (4-2-3-1): Lloris; Trippier, Sanchez, Vertonghen, Davies; Dier, Dembele (Moura 73'); Lamela (Son 64'), Eriksen, Alli (Sissoko 84'); Kane
MANCHESTER CITY (4-3-3): Ederson; Walker, Kompany, Laporte, Delph; Gundogan, Silva, De Bruyne (Toure 89'); Sane (Otamendi 64'), Sterling, Jesus (B. Silva 76')