Born in Bochum to a German mother and a Cameroonian father, Matip began his career with SC Weitmar 45, and was eventually scouted by VfL Bochum in 1997. After several years in VfL Bochum's different youth teams, Matip was scouted by Schalke 04 in July 2000. He made his professional debut on 17 October 2009 in the Regionalliga against 1. FC Saarbrücken, before making his Bundesliga debut on 7 November 2009 against Bayern Munich, in which he scored the game-tying goal. He was subsequently named Man of the match.
On 2 March 2010, Matip signed a three-and-a-half-year contract with Schalke 04.
On 23 February 2013, Matip scored both goals as Schalke secured an important 2–1 victory over Fortuna Düsseldorf, securing the club's second win in 12 games.
In January 2012, Schalke announced that Matip signed a two-year contract extension running until 30 June 2016.
Matip was called up on 23 December 2009 by the Cameroon national football team for the 2010 Africa Cup of Nations but he later on declined to take part in the tournament. It was not yet clear if Matip would represent Cameroon in the future as the German Football Association still hoped that he might represent his country of birth instead. On 6 January 2010, Rainer Adrion announced the annulment of his nomination for the Nations Cup. On 2 March 2010 aged 18, Matip opted to play his international football for Cameroon, after meeting up with the national team ahead of Wednesday's friendly against Italy on 3 March 2010. He made his first national cap in friendly match against Italy and went on to play in the 2010 FIFA World Cup. He was part of the Cameroon national team for the 2014 FIFA World Cup. He played 2 games and scored against the host Brazil, also becoming the first player to score against Brazil in the World Cup hosted in Brazil in 28 years.