Pérez began competitive karting at the age of six and won several national Mexican titles before moving to Europe in 2005 to compete in German Formula BMW. He competed in the British Formula 3 Championship in 2007, winning the National Class championship with T-Sport, before stepping up to the premier International Class in 2008 and finishing fourth in the standings.
Pérez entered the GP2 Asia Series in 2008–09 with Campos Grand Prix, partnering Vitaly Petrov. He became the first Mexican driver to compete at this level of motorsport since Giovanni Aloi raced in International Formula 3000 in 1990. He won his first GP2 race at Sakhir — a lights-to-flag sprint-race victory from pole — and added a second win at Losail during a night meeting in Qatar.
For the main 2009 GP2 Series, Pérez moved to Arden International alongside Edoardo Mortara, finishing twelfth in the standings with a best result of second at Valencia. He then contested two rounds of the 2009–10 GP2 Asia Series for Barwa Addax before committing to a full 2010 main-series campaign with the team. That season he won five races and finished runner-up in the standings behind Pastor Maldonado, a performance that confirmed his readiness for Formula One and attracted the attention of the Ferrari Driver Academy, which he joined in October 2010.
Pérez made his Formula One debut with Sauber in 2011, becoming the fifth Mexican driver in the championship's history. His 2012 season for Sauber was a breakthrough: three podium finishes — in Malaysia, Canada, and Italy — and outstanding tyre management earned him widespread recognition and a move to McLaren to replace Lewis Hamilton for 2013. That season produced no podiums but led to a long-term deal with Force India from 2014.
At Force India and its successor Racing Point, Pérez became one of the series' most consistent points scorers, taking five podiums in his first year with the team and several more in subsequent seasons. He claimed his maiden Formula One victory at the 2020 Sakhir Grand Prix, recovering from last place after a first-lap collision to win the race. Signed by Red Bull Racing in 2021 to partner Max Verstappen, he won at the Azerbaijan Grand Prix and contributed substantially to Verstappen's title bids. In 2022 he achieved his maiden pole position in Saudi Arabia, won in Monaco and Singapore, and finished third in the championship. He was runner-up to Verstappen in 2023 after victories in Saudi Arabia and Azerbaijan. A difficult 2024 campaign ended with a mutual agreement to terminate his Red Bull contract; he returned to the grid with Cadillac in 2026.
Pérez holds Formula One records for the most starts before a first race win (190) and the most races before a first pole position (219), statistics that reflect how long he competed at a high level with machinery below the absolute frontrunners. His GP2 runner-up in 2010 and his consistent conversion of limited machinery into podiums across a long F1 career established him as one of the defining midfield-to-top-team success stories of the turbo-hybrid era.