The former Real Madrid assistant manager starts work immediately after agreeing a two-and-a-half-year contract.
Forty-year-old Karanka, who becomes Boro's first foreign No 1, worked under Jose Mourinho at the Bernabeu and is widely regarded as one of Europe's brightest young coaching talents.
Mourinho has said: "Karanka was my assistant for three years and I know him very, very well.
"I think whatever club gets him, in England or in another country, will be a lucky club."
Boro Chief Executive Neil Bausor said: "We are delighted that Aitor has decided to further his coaching career with Middlesbrough as our Head Coach.
"He brings with him some fantastic experience as a player and as a talented young coach. We are all excited about working with him."
Karanka left Real Madrid in the summer on the arrival of Carlo Ancelloti, who took over from Chelsea-bound Mourinho. Before joining their coaching staff, he was manager of the Spanish U-16 team.
He also represented Real Madrid as a player, making 93 appearances for them between 1997 and 2002 and winning the Champions League with them in 2000 when they beat Valencia 3-0.
The Vitoria-born defender started with Athletic Bilbao and returned for a second spell with the Basque club after leaving Madrid before finishing his career in the USA with Colorado Rapids.
Karanka won a single cap for the Spanish senior team, having played 14 times for their U-21 side.
He also represented Spain in the 1996 Olympic football tournament, where they reached the quarter-finals, and also played for the Basque country team.