Liverpool will host Manchester United in the FA Cup fourth round, Sunderland face Middlesbrough, while Chelsea could be heading to QPR.
United's reward for coming past Manchester City in Sunday's third-round tie is a trip to Anfield to face bitter rivals Liverpool.
Sir Alex Ferguson's men, who overcame 10-man City 3-2 at the Etihad Stadium, will face the Reds on the weekend of January 28 and 29.
United have won the competition 11 times, while Kenny Dalglish's men have triumphed on seven occasions.
The game will be the first meeting of the two sides since the controversial clash in October when Liverpool forward Luis Suarez racially abused United defender Patrice Evra. Liverpool accepted an eight-match ban for the Uruguayan over the incident earlier this month.
Players from United and Liverpool reacted positively to the draw on Twitter.
United defender Rio Ferdinand tweeted: "Liverpool away... what a tie! Great game for the #FaCup + our fans! Let's av iiiiiit! Roll on the 4th round."
Reds midfielder Charlie Adam added: "Great draw man united @ home, that's the FA Cup."
QPR will host west London neighbours Chelsea if they can overcome the MK Dons in a replay at Loftus Road.
Chelsea captain John Terry could make a first return to the ground since he was accused of racially abusing Rangers defender Anton Ferdinand, a matter which has become the subject of a criminal case and an accusation which he strenuously denies.
As well as Liverpool versus Manchester United, there are two other definite all-Premier League ties with West Brom hosting Norwich and Everton welcoming Fulham to Goodison Park.
Arsenal will be at home to Aston Villa if they can overcome Leeds at the Emirates Stadium on Monday night, while Bolton will take on Swansea at the Reebok Stadium if they see off Macclesfield in a replay having drawn 2-2 at Moss Rose on Saturday.
Sunderland's reward for beating Peterborough on Sunday is a home draw against local rivals Middlesbrough, while Newcastle will travel to face the winner of the replay between Wrexham and Brighton.
Black Cats manager Martin O'Neill, reacting to the draw, told ITV1: "It's a tough one but we're at home anyway. I wonder what (former Middlesbrough midfielder) Lee Cattermole thinks of it.
"It will mean something to the supporters who have stayed on here and cheered us off and maybe Lee himself."
Swindon, who upset the odds to knock out Wigan on Saturday, will face a trip to the east midlands in round four to take on either Nottingham Forest or Leicester.
Crawley will take on Hull after the League Two side knocked Championship club Bristol City out on Saturday.
Elsewhere, Championship leaders Southampton will travel to face the winners of the replay between Dagenham & Redbridge and Millwall, Blackpool host Sheffield Wednesday who knocked out West Ham on Sunday, while League One Stevenage, who upset Reading, are at home to Notts County.
Tottenham will make the short trip north to take on Watford, Derby host Stoke and Sheffield United will be at home to the winners of the replay between Wolves and Birmingham at Molineux.
FA Cup fourth-round draw in full:
Brighton/Wrexham v Newcastle
Sunderland v Middlesbrough
Dagenham & Redbridge/Millwall v Southampton
Hull City v Crawley Town
MK Dons/QPR v Chelsea
West Brom v Norwich City
Blackpool v Sheffield Wednesday
Arsenal/Leeds United v Aston Villa
Stevenage v Notts County
Watford v Tottenham
Liverpool v Manchester United
Derby County v Stoke City
Everton v Fulham
Macclesfield/Bolton v Swansea
Sheffield United v Birmingham/Wolves
Nottingham Forest/Leicester City v Swindon Town
Ties to be played on weekend of January 28/29.
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