Liverpool beat City 4-3 at Anfield last time out, but the runaway leaders rarely looked in danger of dropping further points on Saturday, Aguero taking his tally of goals against Newcastle to a whopping 14.
In the first half, the visitors looked like a team whose only plan was to sit back and keep the game goalless for as long as possible.
Aguero doubled his tally for the day from the penalty spot in the second half, but City became sloppy thereafter and Newcastle grabbed a goal back in style through Jacob Murphy.
Further chances fell to Newcastle as they threatened to pull off a shock comeback, yet Aguero killed off their hopes with a fine 83rd-minute finish after Leroy Sane’s incredible solo run, ensuring City again opened up a 12-point lead at the top of the table.
City were all over Newcastle for the entire first half, dominating the ball and keeping their opponents penned into their own defensive third for long periods.
However, arguably the best chance of the opening period fell to the visitors in the second minute, as Christian Atsu’s cross fell kindly for Ciaran Clark, who shot straight at Ederson.
John Stones followed suit in wasting a decent chance soon after, prodding David Silva’s cut-back wide of the right-hand post.
City’s frustration increased when a Raheem Sterling goal was disallowed – correctly – for offside.
But their persistence paid off in the 34th minute, as Aguero got the slightest of touches on De Bruyne’s left-wing cross to find the bottom-right corner.
De Bruyne nearly added a second shortly after, only for Karl Darlow to get down and tip his deflected effort wide.
City’s domination continued into the second half and, although chances hardly flowed, Newcastle’s performance showed nothing to suggest the hosts’ lead was at threat.
The lead was eventually increased in the 63rd minute thanks to Aguero’s powerful penalty, converted after Sterling had been clumsily tripped by Javier Manquillo.
Newcastle pulled one back out of nowhere soon after, though, as Clark’s pass released Murphy behind City’s defence and the winger produced a brilliant finish to chip the approaching Ederson.
The Brazilian nearly gifted Newcastle an equaliser when he spilled shots from Mohamed Diame and Ayoze Perez in quick succession, but City survived and Aguero wrapped things up late on, stroking home left-footed after a remarkable run and cut-back from the excellent Sane.