The spotlight will now switch to who White Hart Lane chief Daniel Levy will turn to as the Portuguese's replacement.
Here, we look at some of the likely candidates.
The veteran Italian was at White Hart Lane on Sunday and his long-time right-hand man Franco Baldini is the club's technical director. Capello is currently the coach of Russia and has a World Cup ahead, but may fancy a shot at the Premier League.
Baldini has plenty of top-level experience, albeit not as a manager. He has served the likes of Real Madrid and England with Capello, and has signed a lot of the Tottenham squad. If he fancies being a manager, this may be his chance.
The Dane is well thought of as a result of the job he has done at Swansea, continuing the good work of previous managers and winning the Capital One Cup last season. Has a reputation for playing good football and would doubtless be a good appointment.
Hiddink is a seasoned trouble-shooter and is currently out of work after a well-travelled and successful career. Has managed in the Premier League before with Chelsea and also has plenty of experience as an international coach.
A former Spurs midfielder, Sherwood would be something of a left-field choice as he has no managerial experience. Works for the club in a technical coaching role and has the benefit of knowing the players.
Roberto di Matteo
Has plenty of experience of picking up the pieces of a Villas-Boas job, having replaced him at Chelsea and going on to win the Champions League with his squad of players. Sacked by Chelsea a year ago and has not worked since, but if Spurs want him they may have to move fast as he is being linked with a move to old club West Brom.