Mason has Sunday’s Carabao Cup Final against Manchester City around the corner, but is still likely to go with his strongest side to build confidence and momentum ahead of the Wembley showpiece.
The absence of Harry Kane, missing with an ankle injury, sees Mason start Heung-min Son up-front, freeing up space for Bale and Giovani Lo Celso in the front four.
Mason’s defensive selections are intriguing after Mourinho all but lost confidence with all his senior centre-backs.
The 29-year-old leaves out Joe Rodon, who impressed in the death-throes of Mourinho’s reign, and brings in Toby Alderweireld and Eric Dier.
Harry Winks will be more confident of minutes now his former teammate is in charge - and is back on the bench - but Tanguy Ndombele and Pierre-Emile Hojbjerg were two of Mourinho’s more consistent players and keep their places in midfield.
Matt Doherty is fit again but doesn’t make the squad. Ben Davies joins talisman Kane on the sidelines.
Tottenham: Lloris, Aurier, Alderweireld, Dier, Reguilon, Lo Celso, Hojbjerg, Ndombele, Lucas, Son, Bale
Subs: Sanchez, Winks, Lamela, Hart, Sissoko, Alli, Bergwijn, Tanganga, Vinicius
Southampton: McCarthy, Walker-Peters, Bednarek, Vestergaard, Salisu, Walcott, Ward-Prowse, Armstrong, Tella, Adams, Ings
Subs: Stephens, Redmond, Djenepo, Minamino, Diallo, N'Lundulu, Forster, Ferry, Jankewitz
Where: Tottenham Hotspur Stadium, Wednesday April 21, 18.00
TV: Sky Sports
Spurs from: Lloris, Hart, Austin, Aurier, Tanganga, Doherty, Reguilon, Dier, Alderweireld, Rodon, Sanchez, Winks, Ndombele, Lo Celso, Dele, Bergwijn, Lamela, Lucas, Son, Bale, Vinicius.
Injury list: Davies (calf), Kane (ankle)
Referee: David Coote
Last meeting: Saints 2-5 Spurs