Cape Town - FA Cup holders Arsenal, who have lifted the trophy a record 12 times, begin their bid on Saturday to become only the third club in history and the first in 130 years to win it three years running.
The Gunners, top of the Premier League, have not lost in the FA Cup since defeat by Blackburn in the fifth round in 2013 and they will seek to preserve that record against Sunderland at the Emirates.
Leicester City, second in the Premier League, face fourth-placed Tottenham Hotspur at White Hart Lane and third-placed Manchester City go to top-flight rivals Norwich City.
Arsenal have only lost once to Sunderland in their last 22 meetings, in an FA Cup fifth-round tie in 2012.
Sunderland boss Sam Allardyce said this week, however, that he will be forced to change his struggling team, accusing the Premier League of devaluing the FA Cup by scheduling league fixtures next week.
"Of course, I'm going to make changes for our Cup tie at Arsenal on Saturday," Allardyce said.
"If you want us to respect the FA Cup, don't put Premier League fixtures on in the midweek just after New Year."
Spurs, the eight-time FA Cup winners who beat Leicester in the 1961 final, will be eager to avenge a 2-1 fourth-round loss to the Foxes last year.
Manchester City face a tricky tie at erratic Norwich after losing 2-1 to Everton in the first-leg of their League Cup semifinal on Wednesday.
Norwich are 15th in the Premier League but they have won three of their last four matches and nearly held City to a draw at the Etihad in October before the hosts sealed a late 2-1 win.
The other all-Premier League ties are Crystal Palace against Southampton, beaten in seven of their last nine matches, and Watford against Newcastle United.
One top-flight club pleased to switch their attention to the Cup will be Aston Villa, last season's FA Cup runners-up, who have not won a league match since the opening day of the season and are bottom of the table.
Besides that win at Bournemouth, their only victory was in the League Cup against midlands rivals Birmingham City and they will be wary of an upset against fourth tier Wycombe Wanderers.
The Merseyside giants both face potential fourth-tier banana skins with Liverpool travelling to Exeter City and Everton facing strugglers Dagenham & Redbridge at Goodison Park.
Premier League champions Chelsea, Cup winners four times since 2007, take on third-tier Scunthorpe United at Stamford Bridge and 11-times winners Manchester United renew an old rivalry with third-tier Sheffield United at Old Trafford.