Pérez was raised in Guadalajara, Jalisco, and began karting at the age of six in 1996. He progressed rapidly through national karting categories in Mexico, repeatedly becoming the youngest driver to win or compete in various classes, and attracted the attention of Escuderia Telmex, the sponsorship programme backed by Mexican telecommunications company Telmex.
In 2004 Pérez competed in the Skip Barber National Championship in the United States. He then moved to Europe, competing in the German Formula BMW ADAC series from 2005. He switched to the British Formula 3 Championship in 2007, winning the National Class title with T-Sport by a comfortable margin. He graduated to the premier International Class in 2008, finishing fourth in the championship. In 2009 and 2010 he raced in the GP2 Series, finishing second in the 2010 standings behind Pastor Maldonado with the Barwa Addax team.
Pérez made his Formula One debut with Sauber in 2011, becoming the fifth Mexican driver to compete in the championship and the first since Héctor Rebaque raced between 1977 and 1981. He was also a member of the Ferrari Driver Academy from late 2010 through 2012. His debut at the Australian Grand Prix was strong in pace, though both Sauber cars were subsequently disqualified for a technical infringement. He finished his first season sixteenth in the championship with fourteen points.
In 2012 Pérez elevated his profile considerably. At the Malaysian Grand Prix he battled Fernando Alonso for victory in the dying laps, closing to within 0.5 seconds before a late error cost him the win; he finished second. He took his maiden podium at the Canadian Grand Prix and a further podium at the Italian Grand Prix, where he rose from twelfth on the grid to second through outstanding tyre management. He finished tenth in the championship with 66 points, earning widespread recognition as one of the best tyre conservers in the field.
Pérez was signed by McLaren for 2013 to replace Lewis Hamilton, ending his Ferrari Driver Academy membership in the process. The season proved difficult; the McLaren MP4-28 was uncompetitive and Pérez's relationship with teammate Jenson Button was strained by several on-track incidents. He achieved a best finish of fifth in India and was released by the team at the end of the season, replaced by Kevin Magnussen.
Pérez joined Force India in 2014 and remained with the team — through its administration crisis and rebrand as Racing Point — for seven seasons. He became a consistent points scorer and occasional podium finisher with the mid-field outfit, scoring five podiums in the Force India era. In 2016 he took podiums at Monaco and Baku and in 2018 added a further podium at Azerbaijan. His management of the team's administration crisis in 2018 was notable; Pérez was among the creditors whose legal action helped force the administration process that ultimately led to Lawrence Stroll's consortium purchasing the assets and preserving the team.
In 2020, his final season with Racing Point, Pérez achieved his most prominent result to that point. At the Sakhir Grand Prix he recovered from last place on lap one following contact with Charles Leclerc to take the lead on lap 64 and win the race — becoming Formula One's 110th race winner and the first Mexican driver to win a Grand Prix since Pedro Rodríguez took the 1970 Belgian Grand Prix fifty years earlier. He finished fourth in the 2020 championship, his best result before joining Red Bull.
Pérez signed with Red Bull Racing for 2021 to partner Max Verstappen. He won at the Azerbaijan Grand Prix that year, taking the lead after Verstappen's tyre failure and holding it through the restart. His defensive drive against Lewis Hamilton in the Abu Dhabi season finale, holding Hamilton long enough for Verstappen to close a significant gap, was credited as a decisive contribution to Verstappen's 2021 championship victory.
In 2022 Pérez achieved his first pole position in Formula One at the Saudi Arabian Grand Prix — on his 215th start, breaking his own record for the most races before a first pole — and won in Monaco and Singapore. He finished third in the championship. In 2023 he won in Saudi Arabia and Azerbaijan and finished runner-up to Verstappen in the World Drivers' Championship, having contributed significantly to Red Bull's dominance throughout the season. Red Bull also won back-to-back Constructors' Championships in 2022 and 2023 with Pérez as a major contributor.
The 2024 season was considerably harder. Pérez was consistently outperformed by Verstappen as the Red Bull RB20 lost its competitive advantage, and multiple high-profile incidents including crashes, penalties, and failures of pace resulted in a final standing of eighth in the championship. By mutual agreement, his contract was terminated at the end of the season and he was replaced by Liam Lawson.
Pérez returned to Formula One in 2026 with the new Cadillac team, signing a contract through at least the end of the 2027 season.
Across fifteen Formula One seasons Pérez has accumulated six race victories, three pole positions, twelve fastest laps, and thirty-nine podium finishes. He holds unique Formula One records for the most starts before a first victory and the most races before a first pole position.