Former Chelsea and Manchester United boss Mourinho was appointed Spurs' new manager on Wednesday after Mauricio Pochettino's departure the previous day.
Spurs moved quickly to begin securing the desired backroom setup for their new manager, as Lille confirmed the departure of Sacramento and Santos.
Tottenham has reportedly paid £3million for the duo, with Sacramento expected to become Mourinho's assistant. Santos joins as goalkeeping coach.
"To Joao Sacramento and Nuno Santos, LOSC wish all the success in this new project," a Lille statement read.
ESPN reports Spurs may yet return to Lille for sporting director Luis Campos, who previously worked with Mourinho at Real Madrid.
Pochettino's time at Tottenham saw numerous reports of tensions between the manager and chairman Daniel Levy over transfers.
The arrival of Campos as sporting director would seemingly act as a buffer, and Mourinho is said to have funds to make signings in January.