He made his debut in state cricket in early 1977, playing for South Australia. He struck five centuries from six innings, becoming one of countless players to strike a century in each innings of a first-class match.
Following this performance, at the age of 21, he was selected to play in the Centenary Test between Australia and England. Players in those days were never paid enough, and it has been reported that Hookes walked out to bat wearing Dunlop Volley tennis shoes. During Australia's second innings he made a score of 56, including hitting English bowler Tony Greig for five consecutive boundaries. He played 23 Test matches, scored one century, and had a batting average of 34.36. He was also involved in the World Series Cricket of the 1970s. In one of these matches, a bouncer broke his jaw, and this marked the beginning of a decline in his career.
After World Series Cricket had finished, Hookes was often selected to play for Australia, but his prodigious talent was never fully realised. His most consistent Test season was 1982/83, where he scored 344 runs at 49.14 against England during the Ashes series, including 4 fifties. He continued his good form against Sri Lanka in April 1983, scoring 143 off 152 balls in Australia's first Test cricket match against that nation. Thereafter his form was patchy, and his last Test was against India in Melbourne, December 26-30 1985, where he scored 42 and 0. This was, coincidentally, Steve Waugh's first Test match.
Despite his failure to live up to expectations at the highest level, Hookes continued to play for South Australia and scored heavily against all opponents. On March 7-8 1987, Hookes and fellow Test discard Wayne Phillips shared in an unbroken 4th wicket stand of 462 for South Australia against Tasmania. Hookes made 306 not out (his highest ever score), Phillips made 213 not out, and poor William Kirkman had bowling figures of 29-0-164-1. In all first class cricket, Hookes scored 12671 runs in 178 matches with an average of 43.99.
After his retirement, he became involved in media commitments, being often quoted in the media, making appearances on television, and hosting a radio program with fellow sportscaster Gerard Healy.
In 2002, he was selected as the new coach of the Victorian cricket team. He led a revival of the team, which had struggled in previous years. The team subsequently rose back to the top of the Australian domestic competition.
On the night of January 18, 2004, Hookes went to the Beaconsfield Hotel in St Kilda, Melbourne with members of the Victorian and South Australian cricket teams, to celebrate a win by Victoria over South Australia in a one-day match. Shortly after midnight, the party was asked to leave the hotel, though there are conflicting stories as to the reason. It is also unclear whether the party left voluntarily or were forced to leave. The security staff continued monitoring the behaviour of the party for a short distance outside the hotel, and there was an altercation. Witnesses gave highly conflicting testimony of what occurred and who started the fight, but what is not in doubt is that Hookes fell to the ground, hitting his head in the process, and going into cardiac arrest. He was revived by paramedics but did not regain consciousness. He was taken to Melbourne's Alfred Hospital and placed on life support. Hookes was taken off life support on the evening of January 19 after family and friends had said their goodbyes, and he died shortly afterwards.
On September 12, 2005, Zdravko Micevic, a security guard and former boxer at the hotel, was acquitted on a charge of the manslaughter of Hookes due to conflicting witness testimonials.. The jury had taken five days to come to its decision, after a two-week trial. Throughout the trial Micevic had maintained that Hookes had without provocation punched him twice, and he felt obliged to defend himself against a further attack. After the trial, Micevic expressed his condolences to Hookes' family and his regret that the incident had ever occurred.