Paes turned professional in 1991. He rose to the number 1 in the world in the junior rankings. In 1992, Paes reached the quarter finals of the doubles event in the 1992 Barcelona Olympics with Ramesh Krishnan. At the 1996 Atlanta Olympics, Paes won the Bronze medal, thus becoming the first Indian to win an individual medal.

Paes was also awarded the highest sporting honour by the Government of India, the Rajiv Gandhi Khel Ratna in 1996. His first successful year in the ATP circuit was when he partnered Sébastien Lareau to reach the US Open doubles semi-final 1993.

From 1996 he started partnering with fellow Indian Mahesh Bhupathi, In the year 1997,Paes and Bhupathi won the semi-finals of the US Open their best grand slam. Paes came to the 14th rank in the doubles from 89 by the end of the year.

In the year 1998, Paes acheived two biggest singles results in the ATP tour. The first one  by winning an ATP singles title and the second was beating Pete Sampras at the New Haven ATP tournament.

In the year 1999, the Paes-Bhupathi duo reached the finals of all the 4 grand slams winning the Wimbledon and the French Open, thus becoming the first Indian pair to win a doubles event at a Grand slam event.
Later that year Paes teamed up with Lisa Raymond to win the Mixed doubles event at Wimbledon and marked his ascent to the No.1 ranking in the doubles.
 
Paes was given the honour of carrying the Indian Flag at the opening ceremony of the Sydney Olympics. Paes was awarded the Padmashri by the Government of India in 2001. The duo won the gold medal at the 2002 Asian Games in Busan.

Leander won the Mixed doubles events at the Australian Open and Wimbledon with Martina Navaratilova, both in 2003.
 His next Grand Slam success was in the U.S. Open doubles event in 2006. Paes lead the Indian tennis team at the Doha Asian Games in 2006 and won two golds in the Men's doubles (partnering Mahesh Bhupathi) and Mixed doubles(partnering Sania Mirza). Paes has maintained his doubles ranking in the top 20 in the world between 2005 and 2007.

 With wins in the Rotterdam and ATP Masters Series in Indian Wells, Paes has taken his doubles tally to 38, as of May 2007. Later in 2008, with Cara Black, he won the 2008 US Open Mixed Doubles title. In 2009, he won the French Open Men's Doubles title with Lukas Dlouhy. In the US Open 2009, Leander partnering with Lukas Dlouhy won the Men's Doubles title beating Mahesh Bhupati and Mark Knowles.