Here, we look at five key issues around the top-of-the-table clash.
JOSE MOURINHO v PEP GUARDIOLA
Where else to start? These two managerial heavyweights loom just as large as local bragging rights on this occasion, giving the battle for Mancunian supremacy a truly global feel.
Portuguese Mourinho has home advantage and the more settled starting XI but he will need no reminding that his head-to-head record against Spaniard Guardiola leaves plenty of room for improvement.
They have met 16 times in total, with Guardiola winning seven times to Mourinho's three alongside six draws
Their first El Clasico match-up ended with a 5-0 win for Guardiola's Barcelona over Mourinho's Real Madrid and the latter will want to resume their rivalry on a better note.
THE YOUNG ONES
Both sides boast talented teenage forwards who have yet to start a game this season but may have a key role in deciding the derby.
United's Marcus Rashford is pushing Anthony Martial hard for a place after scoring the late winner against Hull last time out then scoring a stunning hat-trick for England Under-21s during the international break.
For City, Kelechi Iheanacho is angling to replace the suspended Sergio Aguero
Nobody in the league can match the Argentinian's finishing prowess but Iheanacho is the only other genuine striker in the City ranks.
Raheem Sterling and Nolito can play as false nines, but expect to see the Nigerian forward either from the start or from the bench.
BRAVO'S BOW
Guardiola used up some of his capital with the City fans by ditching their favourite Joe Hart as one of his first acts
Willy Caballero was merely a pawn in the game and new £17million arrival Claudio Bravo is the man earmarked to take the gloves.
He should make his debut in the high-profile battle and Hart's advocates will be paying particularly close attention to how the Chilean fares.
There will be a particular imperative on him to show exemplary distribution, given the reasoning for Hart's exile.
ROONEY'S ROLE
Wayne Rooney found himself in a familiar position this week, with pundits debating his use on England duty.
The Red Devils skipper played in a deep midfield role - apparently at his own prompting - that jarred with the advanced attacking job he has been handed by Mourinho.
Interest in his form, fitness and fallibility never appears to slow down so what better stage for him to make his case than this?
He is the fixture's record goalscorer with 11, and will be aiming to reach a dream dozen at Old Trafford.
CITY'S CENTRAL DILEMMA
With John Stones already established at the heart of the City defence, there is a serious question over who will partner him on Saturday.
Club captain Vincent Kompany is close to fitness but it would be a huge gamble to throw him into such a fixture
Aleksandar Kolarov has been a surprising hit at centre-half early in the campaign yet may find this a step too far.
That leaves Nicolas Otamendi in pole position and he will know chances like this may not come around too often if he does not impress.
Source : PA
Source: PA