Roy Hodgson takes an Eagles side to the Amex for the first time since a Championship play-off semi-final in 2013, as they meet in the top flight for the first time since April 1981.
The Seagulls, despite finding themselves losing to an unlucky deflected goal at Manchester United on Saturday, go into the clash as favourites and sit eleven places above their rivals.
While Palace are still rock bottom of the Premier League, their late win over Stoke will give renewed confidence as they make the 45-mile trip to the south coast.
Where, though, does the rivalry stem from? They are far from local rivals and there are no historical or industrial links between the two. Regular duels in the third division in the 1950s added spice to their meetings, but the hatred can be traced back to an FA Cup tie in the 1970s, and it has been building ever since.
Mullery vs Venables