Patrick Mouratoglou was Serena Williams' coach from June 2012 to 2022. Since spring 2022, Mouratoglou has been the coach of Simona Halep and Holger Rune.

He founded the Mouratoglou Tennis Academy in 1996 and has coached many emerging players, including Marcos Baghdatis, Julia Vakulenko, Anastasia Pavlyuchenkova, Aravane Rezai, Irena Pavlovic, Jeremy Chardy, Laura Robson, Yanina Wickmayer and Grigor Dimitrov.

In March 2012, Mouratoglou began coaching Grigor Dimitrov and began guiding him back into the world's top 100, having dropped to No. 102 when he started. This association ended in September of that year and Mouratoglou moved on to coach Serena Williams.

In 2015, Stefanos Tsitsipas started training in his own tennis academies and was coached by Mouratoglou together with his father Apostolos.

In spring 2022, Simona Halep started training with Mouratoglou. He began coaching up-and-coming youngster Holger Rune in October 2022, in Halep's absence from the WTA Tour due to her doping suspension, and helped lead him to his first Masters 1000 title, defeating Novak Djokovic in the final.