McGuigan started his professional boxing career on May 10, 1981, beating Selwyn Bell by a knockout in two rounds in Dublin.

After another win, he suffered his first setback, losing to Chris Eubank's brother, Peter Eubank by a decision in eight rounds at Wembley. 

In 1985, McGuigan met former world Featherweight champion Juan Laporte and won by a decision in the tenth round. Following one more win, he finally got his world title try when the WBA world featherweight champion, Eusebio Pedroza, came to London to put his title on the line against McGuigan. McGuigan became a world champion by dropping Pedroza in round seven and winning a unanimous fifteen round decision. McGuigan instantly became a national hero and later that year, he was named BBC Sports Personality of the Year. 

Barry retired from boxing in 1989 and currently works as a boxing commentator for ITV. He has tried a hand at acting, appearing in the movie Malicious Intent in 2000, and has written two biographies. 

His record was 32 wins and 3 losses, with 26 wins by knockout. In January 2005, McGuigan was elected into the International Boxing Hall of Fame.