Depailler honed his craft in Formula Two during the early 1970s, competing in events at Pau, the Nürburgring, and Salzburgring. He also raced for the Renault sports car team, though a collision with teammate Jean-Pierre Jabouille at the Nürburgring in April 1976 earned him a three-race suspension from the team. His consistent performances in single-seaters caught the attention of Ken Tyrrell, who selected Depailler alongside Jody Scheckter to replace the retired Jackie Stewart and the deceased François Cevert for the 1974 season.
Depailler's first years with Tyrrell established him as a steady points scorer capable of front-row pace. He captured pole position for the 1974 Swedish Grand Prix in only his ninth Formula One race, and finished second to Scheckter in that event. Over subsequent seasons he gathered multiple podiums — including second places at the 1976 Brazilian, French, and Japanese Grands Prix — without breaking through to a race victory, a streak that lasted an unusually long time. He jointly holds the record for the most podiums (15) accumulated before winning a first Grand Prix.
The breakthrough finally came at Monaco in 1978. Driving a Tyrrell-Ford 008, Depailler secured victory at the 36th running of the Monte Carlo race in his 69th championship start, having finished second there eight times previously. His close calls and persistent near-misses had made the win deeply anticipated. That year he also rose from 12th on the grid to third in the United States Grand Prix West at Long Beach.
For 1979 Depailler moved to the Ligier team, which had switched from the Matra V-12 to a Ford Cosworth V-8 engine in the new JS-11 chassis. He ran second to teammate Jacques Laffite in Brazil and then delivered a flag-to-flag victory at the Spanish Grand Prix at Jarama in May 1979, sharing the championship lead with Gilles Villeneuve with 20 points apiece at the end of April.
His season ended abruptly when he broke both legs in a hang-gliding accident on 3 June 1979 near his hometown of Clermont-Ferrand. His heel was also critically damaged. Because the Ligier team received financial support from the French government — which required that any replacement also be French — Jacky Ickx stepped in for the remainder of the year. Depailler spent months recovering in a Paris hospital, rebreaking one of his fractures after falling out of his hospital bed in early August, but retained ambitions to return the following season.
In 1980 Depailler joined the revived Alfa Romeo Formula One squad. Still managing pain from his previous injuries, he fitted his car with specially adapted brakes designed to build strength in his legs. He showed genuine pace — qualifying third for the 1980 United States Grand Prix West — but reliability was poor. On 1 August 1980, during a private test session at the Hockenheimring ten days before the German Grand Prix, a suspension failure on his Alfa Romeo 179 sent the car into the Armco barriers at the high-speed Ostkurve at approximately 200 km/h. The vehicle overturned and vaulted the barrier. Depailler sustained fatal head injuries and died at the circuit.
As a direct consequence of Depailler's fatal accident, a new chicane was constructed at the Ostkurve of the Hockenheim circuit to slow cars through that section; the modification was first used at the 1982 German Grand Prix. His home city of Clermont-Ferrand honours him with the Mini Circuit Patrick Depailler, one of the oldest model-car racing tracks in France, which hosted an International Federation of Model Auto Racing meeting in 1999. Depailler was portrayed by Xavier Laurent in Ron Howard's 2013 film Rush. His career total of two wins, one pole position, four fastest laps, and 19 podiums reflects a driver who consistently extracted the maximum from equipment that was rarely the fastest on the grid.