The two sides went head-to-head for a place in the Champions League last season. Tottenham finished fourth while the Magpies ended up a place below their opponents.
Both teams are likely to play their new signings as key players are sidelined due to injury. However, Luka Modric has been dropped following his ongoing transfer talks with Real Madrid. Villas-Boas will also miss midfielder Scott Parker but gets a big boost with the return of speedy Welshman Gareth Bale.
New signings Jan Vertonghen and Gylfi Sigurdsson could make their debuts against Newcastle. Tom Huddleston will start along with Brazilian defensive midfielder Sandro.
Toon boss Alan Pardew has more to worry due to injuries to several key players. Midfielders Cheikh Tiote and Yohan Cabaye are yet to be declared fit while Hatem Ben Arfa will miss out due to a knee problem. New signing Vurnon Anita could make the cut but strikers Demba Ba and Papiss Cisse are expected to start.
Trivia: Spurs thrashed Newcastle 5-0 last season. The Magpies recorded their second biggest league win when they beat Spurs 7-1 back in 1996.
Kick-Off 22:00 IST, Sports Direct Arena, Newcastle upon Tyne.
Newcastle United (4-2-3-1): Krul-Simpson, S Taylor, Coloccini, Santon-Anita, Gutierrez-Marveaux, Ba, Cabaye-Cisse.
Tottenham Hotspur: Friedel-Walker, Dawson, Vertonghen, Assou-Ekotto-Sandro, Huddlestone-Sigurdsson, Van der Vaart, Bale-Defoe.