Kek started his professional football career at his home club Maribor in 1979, before moving to the Austrian club Spittal/Drau in 1985, where he spent 3 seasons. He then transferred to another Austrian club, GAK of the Austrian Bundesliga where he played for 7 years. After that he returned to Maribor, where from 1995 to 1999 he won 3 Slovenian league titles, before retiring. He spent most of his career playing in defense, mostly in the centre back position and was known for his leadership abilities.
After finishing his career as a player, Kek stayed at Maribor, serving as an assistant coach for one season, before being appointed manager in 2000. He immediately won the league title in the 2000–01 season. Under his guidance the team won the league again in 2003. In 2006 he was the coach of the Slovenian under-15 and under-16 national football teams. On 3 January 2007, Kek was appointed manager of the Slovenia national team, which he led to the 2010 FIFA World Cup after beating Russia in the play-offs.
The Kek family always had close ties with NK Maribor. Matjaž's father, Franc Kek, played for Maribor during the early 1960s, earning 50 league appearances for the club and scoring one goal in the process. His son Matjaž (born 1991) is also a footballer.