Pep Guardiola could become the first coach to inflict two league defeats upon Jose Mourinho in a single season when they meet in Thursday's Manchester derby.
City host their neighbours at the Etihad Stadium aiming to enhance their chances of finishing in the Premier League's top four this season.
Sitting in fourth place, Guardiola's side occupy the final Champions League spot but sit just one point ahead of United with six games left to the campaign.
Although United got the better of their rivals in the EFL Cup in October, they were beaten at home the previous month as Kevin De Bruyne and Kelechi Iheanacho fired City to a 2-1 victory.
With the likes of Zlatan Ibrahimovic, Paul Pogba and Juan Mata missing through injury, Guardiola could be set to achieve an unprecedented feat this week.
In nearly 17 years as a head coach, Mourinho has never been beaten by the same manager twice in a league season in a career that has seen him lift titles with Porto, Chelsea, Inter and Real Madrid.
However, United have lost just once in their last 20 games in all competitions - suffering an FA Cup defeat to Chelsea - and are on an unbeaten run of 23 matches in the league.
Guardiola, meanwhile, suffered his first double defeat to a single opponent in the league earlier this month when Chelsea beat them 2-1 at Stamford Bridge.