Panis began his career in karting before graduating through French junior single-seater series. He won the Formula Renault championship in 1989, finished second in French Formula Three in 1991, and claimed the International Formula 3000 title in 1993, which opened the door to Formula One.
Panis joined the French Ligier team for 1994 at age 27. He made his debut in Brazil and scored a surprise second place at the German Grand Prix at Hockenheim, finishing 11th in the championship. In 1995, he again secured a surprise second at the Australian Grand Prix and gathered a series of fourth-place finishes to end eighth in the standings.
The defining moment of Panis' career came at the 1996 Monaco Grand Prix. Starting 14th on a wet track, he navigated the attrition masterfully, changing to slick tyres at the optimal moment and overtaking Eddie Irvine for third before both the Williams of Damon Hill and the Benetton of Jean Alesi suffered mechanical failures. Of the field, only three cars finished the race — Panis, David Coulthard, and Johnny Herbert — with Panis first, having held off a late charge from Coulthard. The victory was Ligier's first win in 15 years and the last they would ever achieve. It was also the first French victory in a French car at Monaco in 66 years.
When Alain Prost purchased Ligier and rebranded it as Prost Grand Prix, Panis remained with the team. He began 1997 strongly, taking the tyre manufacturer Bridgestone's first podium at Brazil and standing third in the championship after six rounds. A serious accident at the 1997 Canadian Grand Prix, in which he broke both legs at high speed, ended his season after race nine. He missed seven rounds and was replaced by Jarno Trulli before returning for the final three races. Despite missing half the season, Panis finished ninth in the standings with 16 points.
The 1998 season was disappointing, with the Prost car uncompetitive and the pins still in his legs restricting him. He scored no points across the year. In 1999, improved form returned in flashes, but strategic errors and misfortune limited his tally, and Panis parted ways with Prost after that season.
Panis tested for McLaren in 2000, where his pace impressed the team sufficiently to consider him as a replacement for an injured David Coulthard, though Coulthard recovered in time. This testing exposure earned Panis a drive with BAR for 2001. His best result for BAR was a fourth place at Brazil, and across two seasons he scored eight points, finishing fourteenth in the championship in both years.
Panis joined Toyota for 2003, his ninth season in Formula One. He handled the demands of one-lap qualifying well and provided experienced technical input, scoring six points to finish 15th. He remained for 2004 and retired after the Japanese Grand Prix, having announced his intention to withdraw mid-season. He subsequently worked as a test driver for Toyota through 2006. He was regarded as one of the best test drivers in the paddock, with Mika Häkkinen reportedly upset when Panis left the McLaren testing programme.
Panis returned to active racing in 2008 with Oreca in the Le Mans Series and competed in four editions of the 24 Hours of Le Mans, finishing fifth with Oreca in 2009 and 2011. In 2016 he formed his own sports car racing outfit, Panis Barthez Compétition, alongside former footballer Fabien Barthez, competing in the European Le Mans Series. The team subsequently won the 2025 ELMS LMP2 championship.
Panis is the father of racing driver Aurélien Panis.
Panis is best remembered for the 1996 Monaco victory, a result that captured the unpredictable nature of that circuit and of Formula One more broadly. A steady, racecraft-oriented driver with excellent tactical awareness in attrition races, he never again had the raw machinery to repeat that peak result. His resilience in returning from a double leg fracture in 1997 to finish ninth in the championship that year — and to continue racing for seven more seasons — is a mark of his determination. His longevity in the sport and his transition into team management have made him a continuing figure in French motorsport.