The four clubs boast 28 FA Cup titles between them, with Saturday’s match – between Manchester United and Spurs – representing 20 of those triumphs.
But eight-times winners Spurs have not reached the final, let alone won it, since 1991, while Southampton only success in the competition came back in 1976.
But who will come out on top this weekend?
Scroll down for all the key betting information ahead of the FA Cup semi-finals at Wembley.
Semi-final one | Manchester United vs Tottenham
Photo: Tottenham Hotspur FC via Getty Images
Tottenham Hotspur FC via Getty Images
Head to Head
FA Cup Head to Head
FA Cup titles
Manchester United (12)
Tottenham (8)
1908-09
1900-01
1947-48
1920-21
1962-63
1960-61
1976-77
1961-62
1982-83
1966-67
1984-85
1980-81
1989-90
1981-82
1993-94
1990-91
1995-96
1998-99
2003-04
2015-16
In Pictures | Tottenham vs Manchester United | 31/01/2018