Goals in each half from Son Heung-min and substitute Giovani lo Celso, secured the three points and a fourth straight league win for Spurs, who are two points ahead of second-placed Chelsea.
The victory was the first time Mourinho has enjoyed back-to-back wins over his old rival Guardiola.
Earlier Chelsea had gone top after a 2-0 victory at Newcastle United courtesy of an own goal by Federico Fernandez and Tammy Abraham's second-half effort.
Aston Villa missed a chance to go top after a 2-1 loss to Brighton & Hove Albion, who celebrated their first Premier League victory since September.
Manchester United's risen to ninth after a controversial 1-0 win over West Bromwich Albion at Old Trafford.