Hughes was born in Euroa, Victoria. He started kindergarten while at Apollo Bay and his first year at school came when the family went back to Euroa. Organized sport began in 3rd grade at Werribee. In 5th grade, he pestered his father to be allowed to join football at Werribee where he held his own, despite the fact that he was one of the smallest players when out of his age group. Hughes' enthusiasm for sport was described as "unquenchable."

Hughes started his career playing district cricket with Footscray in 1978–79. Footscray, (now called Footscray-Edgewater), subsequently has had their main home ground named after him; it is now known as the Mervyn G. Hughes Oval. He was selected for Victoria in 1981–82, and made his debut against South Australia.

Hughes first appeared for Australia against India in 1985–1986. He took 1–123 and was not re-selected until the Ashes Series against England the following year.

At Perth, in 1988–89, Hughes completed a hat-trick spread across three separate overs, two innings, and two different days. He had Curtly Ambrose caught behind with the last ball of his 36th over; ended West Indies' first innings in his 37th, by removing Patrick Patterson; and more than a day later, completed his hat-trick by trapping Gordon Greenidge lbw with the first ball of West Indies' second innings.

The Australian selectors always viewed Hughes as a Test match player rather than a one-day player. He was generally only selected for the shorter game when another player was injured or otherwise unavailable.

Hughes' physical presence (a burly 6'4"), handlebar moustache, a penchant for exuberant displays of affection for his fellow players, and a tendency to talk to the opposition in inventively colourful language (his nickname was "Fruitfly" – a somewhat incongruous nickname until Allan Border explained it was a reference to "Australia's greatest national pest"), and a (some would say) "mincing" run-up (that at times stretched to 45 paces), made him a firm favorite amongst supporters, who would often imitate his warm-up stretches behind him en masse. In England, on his second Ashes tour in 1993, the crowd often chanted "Sumo" when he ran in to bowl.

Hughes played his last Test in Cape Town against South Africa in 1994.

Late in his career, Hughes undertook a stint with the ACT Comets, which turned out to be unsuccessful. He claimed only five wickets at an average of 46.80 over six matches (Rodney Davison, Jimmy Maher, Jamie Cox, Shaun Young, and Ryan Campbell).