Chelsea will begin the defence of their FA Cup with a tricky away tie at fellow Premier League club Southampton.
Rafael Benitez's side is in desperate form, having not won a top flight game in eight attempts, and are staring at a group stage exit in the Champions League, which they won last season.
Manchester United also face a difficult away trip, heading to Upton Park to face West Ham, who beat Chelsea 3-1 on Saturday.
Elsewhere, Premier League champions Manchester City start their quest to win the FA Cup for the second time in three years with a home tie to Gianfranco Zola's Watford.
Mansfield Town face a glamour tie at home to Liverpool, while Tottenham host Coventry in a repeat of the 1987 final.
Newcastle travel to Brighton trying to avenge their defeat in the fourth round last season, while Everton will play Cheltenham.