After an intense rivalry while in charge of Real Madrid and Barcelona, the pair met in English football for the first time on September 10, with City winning 2-1 at Old Trafford as Guardiola struck the first blow.
The two were not due to meet again until the reverse Premier League fixture at the Etihad on February 25, but they will now face each other in the week beginning October 24.
Elsewhere West Ham face Swansea after narrowly sneaking past Accrington Stanley in the third round, and Tottenham travel to Reading in two attractive ties.
Arsenal are at home to Reading following their comfortable win at Nottingham Forest while there is an all-Premier League clash between Southampton and Sunderland.
At least two Championship sides will make it through to the quarter-finals after Leeds were paired with Norwich and Newcastle were drawn at home to Preston.
But all eyes will be on Mourinho vs Guardiola when the two Manchester clubs do battle at Old Trafford in October.
FOURTH ROUND DRAW
West Ham vs Chelsea
Manchester United vs Manchester City
Arsenal vs Reading
Liverpool vs Tottenham
Bristol City vs Hull City
Leeds United vs Norwich City
Newcastle vs Preston North End
Southampton vs Sunderland