From the small town of Clones, on the border between Ireland and Northern Ireland, McGuigan became a local hero, fighting at a number of venues in both Ireland and the United Kingdom.  He attracted an enormous and loyal following in the mid-1980s, particularly at the King's Hall in Belfast.  His contribution to peace in Northern Ireland   transcended sport itself and he became a figure of unity amidst the sectarian violence. His maxim 'leave the fighting to McGuigan' epitomised his influence.

In 1985, McGuigan earned his chance to fight for the WBA world featherweight title and he beat Panama’s world champion Eusebio Pedroza in London.  Already a national figure, McGuigan received a hero’s welcome when he returned to Belfast. Later that year he became the first non-Briton to be named Sports Personality of the Year by the BBC TV network. 

He successfully defended his world title twice, against Bernard Taylor and Danilo Cabrera, before losing it in Las Vegas in June 1986 to Stevie Cruz.  After the fight, McGuigan had to go to hospital because of dehydration which had affected him during the contest.  The following year he retired, for the first time, partly because of the death of his father. He used to say his father was his greatest inspiration and, after his death, he felt little reason to continue fighting.

However he made a brief return to the ring in 1988 and 1989 for three non-title fights, before he retired permanently with a record of 32 wins, 26 by knockout, and three defeats. In January 2005, he was inducted into the International Boxing Hall of Fame.

After his retirement, he became involved in TV sports commentary and had a newspaper boxing column. He is an active fundraiser for charities, in particular children's and cancer charities.  The film The Boxer was inspired by his life and he was actively involved in the production, coaching actor Daniel Day-Lewis and choreographing the fight scenes. McGuigan is also Chairman of Fight for Peace, a boxing-based project in the East End of London, supported by the Laureus Sport for Good Foundation, which helps disadvantaged young people.