Luis retired from football in May 2009 having played 127 times for Portugal. He was the most capped player in Portuguese history until passed by Cristiano Ronaldo in June 2016. He was the 2000 European Footballer of the Year and the 2001 FIFA World Player of the Year.

A classic midfield player, Luis was able to beat opponents at will, possessed a powerful free kick and was able to keep his strikers supplied with accurate passes.

He began his club career with Sporting Lisbon before moving to FC Barcelona in 1995 where his career really took off. At Camp Nou, he won a UEFA Cup Winners' Cup title in 1996–97 and successive La Liga titles. He played 172 times for Barcelona, scoring 30 goals, before being transferred to Real Madrid for a record €60 million in 2000.

His arrival at the Bernabeu marked the beginning of the Galactico Era there and he was a member of the team which won the La Liga title in 2001 and 2003 and the 2002 UEFA Champions League. He moved to Internazionale of Milan in 2005 on a free transfer, eventually retiring in 2009, the day Inter won the 2008/09 Serie A title.

Luis made his debut for the Portuguese national team in October 1991, when just 18, and played at the highest level throughout his career, playing in the European Championship in 1996, 2000 and 2004 and in the FIFA World Cup in 2002 and 2006.

He became a Laureus World Sports Academy Member in 2015 and is also an ambassador for the Stop TB Partnership in the fight against tuberculosis. He works closely with Inter Milan, serving as an ambassador for the club. He is also a board member of the Inter Campus charity project run by Inter.