Danilo gave the champions the lead in the first half, but Huddersfield held their own for much of the opening 45 minutes, and it was not until the second half that City showed something close to their best.
Two goals in as many minutes from Raheem Sterling and Leroy Sane took the game away from the hosts, though, as Man City responded to Liverpool's victory over Crystal Palace yesterday with a comfortable triumph of their own.
Pep Guardiola's side have now scored 24 goals in five successive wins so far this calendar year, whereas Huddersfield fall to a 16th league defeat of the season in what was their first outing since parting company with manager David Wagner.
The visitors did make an ominous start to the game, though, and Sergio Aguero skewed one effort off target after only three minutes as City looked for an early opener.
Huddersfield's main problem all season has been putting the ball in the back of the net, and it was a similar story again this afternoon with Adama Diakhaby squandering their first half-chance when he directed a stooping header wide.
It was City's 100th goal across all competitions and Fernandinho almost provided number 101 with an unmarked header from a corner moments later, but City uncharacteristically failed to push on for more goals in an under-par first-half display.
Elias Kachunga forced a routine stop from Ederson as Huddersfield grew into the game, and Guardiola was visibly annoyed by the lack of intensity in his side's performance.
Ilkay Gundogan fired a couple of shots off target towards the end of the first half, but it was not until after the interval that they were able to take the game out of Huddersfield's reach with a quickfire double.
Sane was heavily involved in both goals, creating the first for Sterling by firing a cross into the middle which left the England international with a simple diving header finish from close range.
Sane then got his own name on the scoresheet two minutes later when he latched on to Aguero's layoff before keeping his composure to sweep his finish past Lossl, effectively killing the game off once and for all.
A fourth goal almost followed soon after when Kevin De Bruyne was picked out by Danilo inside the area, but the Belgian could only float his header over the crossbar.
The visitors were able to take their foot off the pedal for the final half an hour, and it was not until four minutes from time that they created another clear chance to add to their advantage when Bernardo Silva was thwarted by Lossl.
Huddersfield had a couple of chances to grab a late consolation too, but Steve Mounie first saw his header well saved by Ederson before slicing a golden opportunity wide from the edge of the six-yard box with the final action of the match.
The Terriers have still only scored 13 goals all season and end the weekend bottom of the table with 10 points now separating them from safety having picked up just one point from their last 10 league games.
HUDDERSFIELD (4-5-1): Lossl; Smith, Schindler, Kongolo, Lowe; Kachunga, Puncheon, Hogg, Bacuna (Pritchard 64'); Mbenza; Diakhaby (Mounie 59')
MAN CITY (4-3-3): Ederson; Walker, Otamendi, Laporte, Danilo; De Bruyne, Fernandinho (D Silva 59'), Gundogan (Delph 80'); Sterling, Aguero, Sane (Bernardo 72')