Busuttil started his career with Rabat Ajax and won 2 titles there. He then went on to have a short one year spell at Verbania Calcio in Italy, where he was capped 20 times and scored 8 goals. He then moved on to spend 6 years playing for Belgian Club FC KRC Genk (322), four of them as captain, and finishing as the club's top scorer for three seasons. In 1994 he returned to play for the Maltese club Sliema Wanderers, where he scored 78 goals, helping his team to win the Maltese Premier League and also the Maltese Cup. He was capped 113 times for the Malta national football team and was their top scorer with 23 goals, until recently Michael Mifsud broke Busuttil's record.
He is known as 'Il-Bużu', an abbreviation of his surname. After he retired, he was football coach at a couple of respected Maltese private schools, most notably St. Michael's Foundation for Education. He then formed his own youth training academy, The Buzu football school. In November 2003, to celebrate the 50th anniversary of UEFA, he was selected as the Golden Player by the Malta Football Association as the most outstanding player of Malta in the last 50 years. Busuttil has also won wider acclaim. In 2000 he received the prestigious Order of Merit of the Republic from the then president of Malta, Professor Guido de Marco, for his contribution to Maltese sport.
As a coach, Busuttil had a stint with the Maltese Football League side Pietà Hotspurs, and assisted Horst Heese in the guidance of the Maltese national team between 2003 and 2005. He return to the position in 2009 as assistant to John Buttigieg. They are both on a 5-year contract. However, in 2011, they were both sacked and replaced by the Italian Pietro Ghedin.