The Reds must overcome a replay to face their Premier League rivals while the ex-Red Devils man could face his former club if they beat Northampton
A tantalising trip to Stamford Bridge to face Chelsea will await Liverpool if they defeat Shrewsbury Town, while Wayne Rooney could be poised for a reunion with Manchester United following the FA Cup fifth-round draw.
The Champions League holders must overcome a replay at Anfield following their 2-2 draw with the Shrews on Sunday, while ex-Red Devils favourite Rooney must first guide Derby County past a rematch with Northampton Town.
Holders Manchester City meanwhile will face a trip to Sheffield Wednesday, while Norwich City have set up an all-Premier League tie against the winners of Southampton and Tottenham’s replay.
The draw, held ahead of Arsenal’s trip to Bournemouth in the final match of the round, included 23 sides, two more than last season, and was conducted by Glen Johnson and Teddy Sheringham.
Fixtures will take place between March 3 and 5, with winners in line to take home £360,000 ($470,000) in prize money from the FA Prize Fund.
For the first time, the round will be played in midweek following the introduction of the mid-season break, with no replays in the instance of a draw.
If sides are level, then the typical route of extra-time, followed by penalties, will decide a victor.
At least seven Premier League sides will be seeking to stake a claim to reach the quarter-finals, with that number potentially rising to nine if both Liverpool and Newcastle United can negotiate their replays.
For the third year in a row, the last 16 could feature representation from all four flights of the English Football League too, with League Two side Northampton still in the mix after they forced a replay against Championship outfit Derby.
The lowest-ranked team who will definitely be playing are League One play-off chasers Portsmouth, who have been rewarded with a clash against either the Cherries or the Gunners following their 4-2 triumph over Barnsley.
Elsewhere, second tier leaders West Brom will look to back up their win over Premier League side West Ham United with a home clash against either Newcastle or Oxford United.
Meanwhile, Sheffield United will make the trip to either Reading or Cardiff City, while Leicester have been handed a Midlands derby with either Coventry City or Birmingham City.
With four different winners in the last four seasons, the sport’s oldest knockout tournament has seen success shared between current holders City, along with their local rivals United, plus Arsenal and Chelsea in recent years.