The Germany international had already agreed a move to White Hart Lane on a Bosman move in the summer, but will now move immediately for a fee of 1.5 million pounds.
The Germany international had already agreed a deal to move to White Hart Lane at the end of the season, but Spurs have been keen to tie up a permanent deal this month.
Brazilian midfielder Sandro has been ruled out for the rest of the season through a knee injury, leaving Andre Villas-Boas short of numbers in the middle of the park.
Schalke had rejected several bids from Tottenham throughout the month for the playmaker, who is the captain of Germany's Under-21 side, although a deal has now been struck.
Holtby has scored four goals in 25 appearances for the Konigsblauen this term.