Gendebien was born on 12 January 1924 in Brussels, Belgium. Before becoming a racing driver, he worked as a forester in the Belgian Congo. In 1952, he returned to Europe and began competing in rallying events.
Gendebien's breakthrough in racing came in 1954 when he won the Tulip Rally driving an Alfa Romeo 1900 TI. He continued to achieve success in rallying, winning the Liège–Rome–Liège Rally, Dolomites Gold Cup Race, and Rally Stella Alpina in 1955, driving a Mercedes-Benz 300 SL. His performances caught the attention of Enzo Ferrari, who signed him to compete in Formula One and sports car events for Ferrari in 1956.
Gendebien made his Formula One debut at the 1956 Argentine Grand Prix. He scored his best finishes in 1960, taking second place at the French Grand Prix and third place at the Belgian Grand Prix, driving for the British Racing Partnership's Yeoman Credit Racing team. However, his success was marred by the death of his teammate, Chris Bristow, during the Belgian Grand Prix.
One of Gendebien's most notable incidents occurred during practice for the 1961 United States Grand Prix, when his Lotus-Climax flipped over, causing him to suffer slight injuries. He also experienced a significant crash in 1958, during the Grand Prix of Buenos Aires, where Argentine Maserati driver Jorge Magnasco died.
Gendebien retired from racing in 1962, at the age of 38, following his fourth victory at the 24 Hours of Le Mans. His wife, Marie-Claire, was killed in a car accident in 1965. Gendebien passed away on 2 October 1998, at his home in Les Baux-de-Provence, southern France.
Gendebien's record of four 24 Hours of Le Mans victories stood until 1981, when Jacky Ickx won his fifth Le Mans title. He also won three 12 Hours of Sebring and three Targa Florio events. Gendebien's legacy is marked by his elegant and discerning driving style, which earned him the respect of his peers and the admiration of Enzo Ferrari.
In addition to his Formula One career, Gendebien competed in various sports car events, including the 24 Hours of Le Mans, 12 Hours of Sebring, and Targa Florio. He won numerous events, including the Tour of Sicily, Tour de France Automobile, Reims 12 Hours, and 1000 km Nürburgring.
Gendebien was appointed to the Order of the Crown of Belgium by King Albert II in 1998. He was also honoured with a turn named after him at the 12 Hours of Sebring, in recognition of his three wins at the event.