Depailler finished 0.9 seconds behind Peter Gethin in the 1972 Formula Two Pau Grand Prix, battling closely in a March 722 over the 70-lap course through the French city; both drivers lapped the field twice. In April 1973 he came third in a Formula Two race at the Nürburgring, driving a Ford Alpine. In May 1974 he qualified first for the Formula Two Pau Grand Prix in his March. In June 1974, during time trials for a Formula Two race at Salzburgring, he crashed his March 742 through a guard rail; Depailler was uninjured but qualifying was halted to replace a section of railing torn off in the accident.
In April 1976, the Renault sports car team suspended Depailler for three races after he was involved in a crash at the Nürburgring that eliminated both his car and the Renault of teammate Jean-Pierre Jabouille. The incident occurred on the second turn, slightly more than a mile into a 180-mile (290 km) race; Depailler lost control and Jabouille crashed attempting to avoid him. The drivers had been instructed not to contest the lead with each other.
Tyrrell gave Depailler drives at France and Watkins Glen in 1972; using one of the older cars, he finished seventh at the latter. In December 1973 he was chosen alongside Jody Scheckter to drive for Tyrrell, replacing the deceased François Cevert and retired Jackie Stewart.
Depailler captured pole position for the 1974 Swedish Grand Prix — his ninth Formula One race — negotiating the 2.49-mile (4.01 km) Anderstorp course in 1 minute 24.758 seconds for an average speed of 105.8 mph. He finished second in that race behind Scheckter, his only podium of the year. In January 1975 he was given 25–1 odds of becoming the 1975 Formula One World Champion. He finished fifth in the 1975 Argentine Grand Prix in Buenos Aires and third in the 1975 South African Grand Prix at Kyalami, staying behind second-place finisher Carlos Reutemann throughout the 78 laps. During first qualifying for the 1975 United States Grand Prix at Watkins Glen, Depailler crashed his Tyrrell into a catch fence; he was not injured.
Depailler finished second in the 1976 Brazilian Grand Prix at Interlagos, ending up second to Clay Regazzoni in qualifying on the second day with a speed of 87.31 mph (140.51 km/h). He gained a third-place finish in that race but drew the ire of rival James Hunt, who went out on the fourth lap claiming Depailler had forced him off the track. Depailler, wrestling with brake trouble, said he did not see Hunt in his mirrors. He placed his six-wheeled Tyrrell third on the grid for the 1976 Monaco Grand Prix; the Tyrrells of Scheckter and Depailler were the only cars able to stay on the same lap as Lauda's Ferrari.
Depailler was second to Hunt in the 1976 French Grand Prix at Le Castellet. Hunt held off a determined Depailler at Mosport Park in the 1976 Canadian Grand Prix; both drivers were ill at the conclusion, with Depailler having inhaled fumes over the last third of the race and losing consciousness after pulling off at the first corner following the finish, though he regained consciousness momentarily. At the 1976 Japanese Grand Prix at Fuji Speedway, Depailler finished second despite tyre problems as the track dried from heavy rain, finishing ahead of Hunt — who secured the 1976 Drivers' Championship by finishing third.
Depailler skidded off the Interlagos track at São Paulo in the 1977 Brazilian Grand Prix and was hospitalised with a leg injury. He qualified 12th for the 1977 United States Grand Prix West. In December 1977 he was promoted to Tyrrell's number one driver when Ronnie Peterson left for Lotus; at the same time Tyrrell revealed it was abandoning its six-wheeled Formula One car experiment.
He finished third in the 1978 Argentine Grand Prix in an Elf-Tyrrell. At the 1978 South African Grand Prix at Kyalami, Peterson passed Depailler on the last turn of the last lap — erasing a 9-second gap after Depailler's car ran short of fuel. Depailler climbed from 12th on the grid to third in the 1978 United States Grand Prix West. He then secured his first Formula One triumph, winning the 1978 Monaco Grand Prix at the wheel of a Tyrrell-Ford 008; it was his first victory in 69 championship races, despite having been second eight times.
For 1979, Depailler switched to Ligier, which began fielding cars with Ford Cosworth V8 engines rather than the French-built Matra V12 engines of 1978. In January 1979 Ligier team manager Gerard Ducarouge described the JS-11's development: the JS-9 had been tested as a wing car following the 1978 United States Grand Prix West, but wind tunnel results were unsatisfactory; the JS-11 was built and tested in December 1978 with positive results, with its new body features revealed at the 1979 United States Grand Prix West.
Depailler led the first ten laps of the 1979 Argentine Grand Prix before engine problems forced a pit stop; he managed a fourth-place finish. He came second to victorious teammate Jacques Laffite in the 1979 Brazilian Grand Prix, Laffite finishing more than five seconds ahead. Depailler made contact with the fence at "Barbecue Bend" in the 1979 South African Grand Prix.
He posted a flag-to-flag victory at Jarama in the 1979 Spanish Grand Prix — his second Formula One win — which enabled him to tie Gilles Villeneuve for the lead in the Formula One world championship standings at the end of April with 20 points each. He qualified third for the 1979 Monaco Grand Prix on a staggered grid.
In June 1979, Depailler was replaced by Ligier following a hang gliding accident on 3 June near his hometown of Clermont-Ferrand in which he broke both legs and critically injured his heel. Because Ligier was receiving financial support from the French government — which required his replacement also to be French — the veteran French-speaking Belgian driver Jacky Ickx took his seat. Depailler fell out of his hospital bed in early August, rebreaking one of the fractures. On 29 August he said he was "resigned not to race again until next year", though he expected to leave his Paris hospital by the end of that week. He had undergone multiple operations on his legs but hoped to attend the autumn North American rounds at Montreal and Watkins Glen as a spectator.
In 1980, Depailler joined the newly formed Alfa Romeo team on its comeback. He had worked his way back from the hang-gliding accident and equipped his car with special brakes designed to strengthen his leg muscles; he was still driving in pain at the time of his fatal accident. The car qualified third for the 1980 United States Grand Prix West but proved unreliable.
Depailler suffered a fatal accident during a private testing session at the Hockenheimring on 1 August 1980, ten days before the 1980 German Grand Prix. A suspension failure pitched his Alfa Romeo 179 into the Armco barrier at the high-speed Ostkurve, inflicting fatal head injuries when the car overturned and vaulted the barrier; it skidded along the top of the guard rail for several hundred feet before flipping onto its roof.
Following his death, a new chicane was built into the Ostkurve at the Hockenheim circuit to slow cars through what had previously been a flat-out curving right-hander. The new Ostkurve Schikane was first used during the 1982 German Grand Prix. A radio-controlled car racing circuit, the Mini Circuit Patrick Depailler — one of the oldest tracks in France — is named in his honour in his hometown; it hosted an International Federation of Model Auto Racing (IFMAR) meeting in 1999. Depailler was portrayed by Xavier Laurent in the 2013 film Rush, directed by Ron Howard. He achieved two wins, one pole position, four fastest laps, and 19 podiums in Formula One.
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