Manchester United, record 10-times winners of the competition, visit Aston Villa in a plum third round match-up, while another glamour tie sends Liverpool to renowned giant-killers Yeovil.
Arsenal, who defeated Southampton 1-0 in last season's final to lift the trophy for the ninth time, will not want to slip up despite chasing glory on four fronts.
Arsene Wenger's side, one point behind champions United going into the second half of the season, are also through to the last 16 of the Champions League and the League Cup semi-finals.
They have not lost to domestic opposition this season but will be wary of a Leeds side who have improved under caretaker boss Eddie Gray, despite a 3-1 reverse at Wolverhampton Wanderers on Saturday that kept them in the relegation zone.
The teams last met in the Cup in the 1996-1997 season when a goal from Rod Wallace gave Leeds a 1-0 win in a fourth-round tie at Highbury.
United's trip to Villa Park will evoke memories of the thrilling third-round encounter at the same ground in the 2001-02 season when Alex Ferguson's side came back from the dead to win.
Villa were cruising at 2-0 up before United scored three times in a five-minute spell late in the game -- including two goals from Ruud Van Nistelrooy in his first FA Cup tie -- to complete an epic comeback.
GIANT-KILLERS
There are three other all-premier league clashes. Last season's beaten finalists Southampton take on Newcastle United, Birmingham City are at home to Blackburn Rovers and Manchester City entertain Leicester City.
Liverpool will need no reminding that third division Yeovil are the most famous of all FA Cup giant-killers, having beaten 20 league clubs before being promoted to the football league in 2003.
Yeovil will earn a cash windfall from the televised game and will have nothing to lose at their Huish Park home.
Liverpool captain Steven Gerrard is a major doubt for the game after suffering a thigh injury in the 2-2 draw at Manchester City on Sunday.
As ever in the world's oldest cup competition there is the potential for upsets, particularly at White Hart Lane where struggling Tottenham Hotspur take on first division Crystal Palace.
Spurs ended the year in the bottom three after four consecutive league defeats and an early exit from the competition they have won eight times would increase the pressure on caretaker boss David Pleat.
Palace defeated Liverpool at Anfield last season before losing to Leeds United in the fifth round and should travel across the capital with plenty of confidence.
Everton also face a stern test from first division leaders Norwich City while Wolverhampton, bottom of the premier league, visit Kidderminster Harriers of the third division.
Two minor league sides, both from the Conference -- one promotion away from England's division three -- have reached the third round.
