With just three games to go, the Terriers sit precariously three points and two places above the relegation drop zone.
Meanwhile, with the title already sown up, Pep Guardiola's side are looking to break records – needing just one more win to claim the accolade of accruing the most points gained in a single Premier League campaign.
The two sides have played some memorable matches over the years – have a look below at five of the best encounters between them...
Manchester City 10-1 Huddersfield Town - November 7, 1987 - Division Two
Unfortunately Town fans will remember this fixture as the team's worst debacle since entering the league in 1910, while City will celebrate it as their biggest win.
As well as losing by such a wide margin, to rub salt into Town's wounds three City players grabbed hat-tricks in their Maine Road demolition - Paul Stewart, David White and Tony Adcock.
A consolation penalty from Andy May in the 88th minute was nothing short of embarrassing for Town, who unsurprisingly ended the season bottom of the table.
Manchester City 0-1 Huddersfield Town - November 7, 1997 - Division One
On the 10th anniversary of the 10-1 debacle, Huddersfield Town exacted bittersweet revenge against a beleaguered Manchester City side.
A Rob Edwards' wonder strike in the 14th minute sealed an unlikely victory for a Terriers side who, even with the three points, remained bottom of the table.
The result led to open rebellion amongst the City supporters with choruses of "You're not fit to wear the shirt" ringing out during the match and protests at full-time calling for the resignation of their chairman Francis Lee.
Manchester City 0-1 Huddersfield Town - November 27, 1999 - Division One
The last time Huddersfield Town beat Manchester City was in their own back yard back in 1999.
A goal from Chris Beech gifted Town all three points and shocked City, who had previously gone unbeaten in 10 games.
The loss would act as a temporary stumbling block for the Citizens, who went on to lose the next two games, before eventually getting back to winning ways and gaining promotion to the Premier League at the end of the season.
Huddersfield Town 0-0 Manchester City - February 18, 2017 - FA Cup 5th round
The FA Cup tie was the first time the two teams had met since February 2000 and it was clear City didn't quite expect the fight Town put up.
Despite Guardiola's side claiming the majority of possession, the Terriers were resolute, refusing the likes of Sergio Aguero and Jesus Navas - and even mustering eight shots themselves.
Manchester City 5-1 Huddersfield Town - March 1, 2017 - FA Cup 5th round replay
Unbeaten in seven, a much-changed Town side pushing for Premier League promotion gave their hosts an early scare when Harry Bunn opened the scoring in the seventh minute.
However, Town were - rather dramatically - brought back down to reality after 90 minutes of bullying from City's attack with Aguero, Leroy Sane and Pablo Zabaleta all grabbing goals in the space of eight first-half minutes.
And if that wasn't enough, Aguero went on to double his tally with Kelechi Iheanacho scoring in the last minute to make it 5-1 to the hosts.