The 25-year-old was recently cleared to return to football after his doping ban was resolved with the English FA and World Anti-Doping Agency (WADA).
Chelsea made Mudryk available for loan to get him back up to speed, with first-team opportunities at a premium under Xabi Alonso this season.
Tottenham have now confirmed Mudryk’s signing, marking the first time a player has moved between the two clubs since Carlo Cudicini in 2009.
It’s also been widely reported that the deal includes a massive £75 million option to buy.
Mudryk has now joined up with former manager Roberto De Zerbi, who gave him his big break during their time at Shakhtar together.
Speaking to Tottenham’s website, Mudryk said: "It's a great feeling. I can't wait to start training and playing for the club, and I'm so excited to be reunited with Roberto De Zerbi.
"I'm a player who brings speed and creativity, and I want to help in both the offensive and defensive areas. I want to make the fans excited.
"I can see it's a strong squad here with good players, and I'm looking forward to sharing a pitch and special moments with them."
De Zerbi added: "Having worked with Misha earlier in his career, I know exactly what he can bring to our team.
"He has the quality to change a game with his speed and ability in one-vs-one situations, and is an exciting, attacking talent.
"I will demand a lot from Misha, and it is our job to help him find the best version of himself. If we do that, then he can become a very important player for us. I am very happy he chose to come here, and I cannot wait to work with him again."