Chelsea will host Manchester City in the FA Cup fifth round.
League One side Shrewsbury Town, the lowest-ranked team remaining, will welcome Manchester United to the Greenhous Meadow.
Holders Arsenal will take on Hull in a repeat of the 2014 final, while Crystal Palace visit Tottenham and Bournemouth host Everton in two all-Premier League clashes.
The ties will be played on the weekend of 19-22 February.
The other games see Watford take on Leeds United, Reading face West Brom, and Blackburn host West Ham.
But it is the tie between the two most recent Premier League champions - described by Chelsea manager Guus Hiddink as a "huge game" - that will attract most attention.
"It's already a final!" the Dutchman added.
It is a third successive away draw against Premier League opposition for Manuel Pellegrini's side.
Meanwhile, Arsenal and Hull meet for the third year running, with the Gunners having eliminated the Tigers with a 2-0 win in the third round last year.
Full FA Cup fifth-round draw:
Chelsea v Manchester City
Reading v West Brom
Watford v Leeds United
Shrewsbury Town v Manchester United
Blackburn v West Ham
Tottenham v Crystal Palace
Arsenal v Hull
Bournemouth v Everton