ESPN reported on Monday that former Spurs midfielder Mason, 29, was likely to assume control alongside Chris Powell as the search for a new manager begins and the club released a statement on Tuesday morning confirming the news.
It read: "Following the departure of Jose Mourinho, we can now confirm that Ryan Mason will take charge as Interim Head Coach for the remainder of the season."
Mason, who was forced to retire as a footballer aged 26 due to a serious head injury, becomes the youngest manager in the Premier League and his first game takes place on Wednesday when Spurs host Southampton.
He had previously occupied the position of Under-19s head coach before becoming Head of Player Development last August.
Speaking ahead of the Southampton clash, he told a news conference he had received well wishes from former Spurs manager Mauricio Pochettino.
"We exchanged a couple of messages and a couple of the other coaching staff from his team as well," Mason said. "He is very busy, understandably, but we have always had a great relationship.
"Listen, he loves this club as well. He wished me all the best and I'm sure we'll be in contact in the future as well."
Mason has been asked to step up after Mourinho was axed along with his coaching staff comprising Joao Sacramento, Nuno Santos, Carlos Lalin and Giovanni Cerra in a move that sources claim cost in the region of £20 million.