The 23-year-old defender has signed a three-year contract with the Magpies and has joined up with Rafa Benítez and his new team-mates at the club's training camp in Ireland.
Madrid-born Manquillo started his career with Atlético, while he has also played on loan for Liverpool, Marseille and Sunderland. As well as representing his country at every youth level, he has Champions League and Europa League experience.
Winger Jacob Murphy joined Newcastle on Wednesday while Ghana international Christian Atsu and French centre-back Florian Lejeune have also signed for the club during the current transfer window.
Speaking about his move, Manquillo said: "I'm very happy to be here. From the first moment that Rafa Benítez called me, I just knew that I had to come here, to such a big club.
"I'm very happy with the challenge ahead.
"I've come here to work hard and give everything on and off the pitch. Hopefully then everything will go in the right direction."
Manager Benítez added: "Like Jacob Murphy, Manquillo is another young player. He can play both sides of the defence and he has a lot of motivation because he knows he has a point to prove.
"He can still improve but he has played for Spain at under-21 level and that is because he is a good player, so hopefully he will show that form here."