De Castella is of Swiss-French descent. He was born in Melbourne, Victoria, the eldest of seven children. Sport was a way of life in his family – his father Rolet ran marathons in his fifties. His mother Anne was a state-level tennis player. His brother Nicholas, took part in four World Cross Country Championships, whereas brother Anthony competed in running at club level for more than 25 years. Rob de Castella was an outstanding track athlete as a teenager and trained under Pat Clohessy from the age of 14.
De Castella first came to international attention when he won the 1981 Fukuoka Marathon in a time of 2:08:18, which was the fastest time recorded for an out-and-back course. It was not initially known to be a world best time, because his time was 5 seconds slower than the time set by Alberto Salazar in the 1981 New York City Marathon. It later emerged that the New York course was about 148 metres short. De Castella's time was later ratified as the world record.
De Castella was the favourite to win the marathon at the 1982 Commonwealth Games in Brisbane. At the start of the race, TanzaniansGidamis Shahanga and Juma Ikangaa raced to the lead and were 50 m ahead of the pack after five minutes. After the 20 km mark, this gap had widened to several hundred meters. By the 23 km mark, Ikangaa had taken the lead from his compatriot, with de Castella in the main pack some 250 m behind, but closing. de Castella passed the now tiring Shahanga at the 38 km mark, and in the next kilometre drew level with Ikangaa then took the lead. However Ikangaa was not done yet, and re-took the lead slightly. The duel continued for the remainder of the race. Eventually de Castella pulled away, and won by 80 m in a time of 2:09:18, 12 seconds ahead of Ikangaa. Briton Mike Gratton finished third in 2:12:06, and Shahanga faded to finish 6th. The race finished on the streets of Brisbane, not in the main stadium.
De Castella won the 1983 Rotterdam Marathon won in 2:08:37, defeating a deep field that included the previously unbeaten Alberto Salazar and Carlos Lopes. The race was also televised live back to Australia. De Castella's time was, at that point, the fourth fastest in history.
De Castella was the favourite for the 1984 Summer Olympics marathon. He ran comfortably in the main group until about 33 kilometres, when he slowed down to drink water. At the same time, the leading runners picked up speed and de Castella suddenly found himself out of contention. He accelerated during the final kilometres to finish fifth.
In addition to marathon running, de Castella was also an accomplished cross country runner. He won the Australian national title once as a junior and four times as a senior, along with five other podium finishes. He competed eight times at the World Cross Country Championships from 1977 to 1986, finishing in the top 20 five times.
De Castella failed to finish the marathon at the 1987 World Athletics Championships. and never again placed very well in a major marathon. He represented Australia at the 1988 Seoul and 1992 Barcelona Olympics, competing in four straight Olympic Games. He finished in the top ten in three Olympics, but never won a medal.
He retired from the sport in 1993 and lives in Canberra, together with his wife Theresa and four children. Previously he was married to the former champion triathleteGaylene Clews. He lost his family home, along with many of his medals and other citations, in the 2003 Canberra bushfires. Choosing to move rather than rebuild, he now lives in a nearby suburb. He later helped with the taskforce established for the reconstruction of areas worst affected by the fires.
From 1990 to 1995, de Castella was the director of the Australian Institute of Sport and subsequently became executive director of Focus On You, a company focusing on corporate and community health and fitness. He has also been actively involved in other organisations dedicated to encouraging healthy living for both children and adults. He also fronts the Indigenous Marathon Project. In 2014 he was made an Officer of the Order of Australia at the Australia Day honours.
In 2003, de Castella launched "deeks", a specialist chain of grain and gluten free bakeries & cafés. In 2004, he earned a black belt in the traditional Okinawan Goju Ryu; he has also been part of a long-running advertising campaign for the multi-vitamin tablet "Centrum".
2014 – Officer of the Order of Australia for distinguished service to the community through programs promoting children's health and fitness, as a supporter and mentor of young Indigenous men and women, and to marathon running.