Kilrea played his first major junior season with the Hamilton Tiger Cubs in 1954–55. In his playing career he played only 26 NHL games, although he had great success in the minor leagues. Kilrea spent four seasons with the Troy Bruins of the IHL, where he was named a second team All-Star in 1958–1959. Most of Kilrea's career was spent with the AHL's Springfield Indians, where he was a multiple All-Star and the franchise's career leader in assists. He has been named to the Springfield Hockey Hall of Fame. Kilrea played under Eddie Shore and credits Shore with teaching him many things that he took into his coaching career.
Kilrea returned to the NHL, briefly, with expansion in 1967. Kilrea has the distinction of scoring the first-ever goal for the NHL Los Angeles Kings. It was during his time with the team's AHL franchise, however, that the roots for what would become the National Hockey League Players Association would arise, as a direct result of the efforts of Kilrea and Alan Eagleson, then the agent for Bobby Orr.
After ending his playing career, Kilrea started coaching minor hockey in Ottawa. He first made a name for himself when his Ottawa West Midget AA team defeated a touring Soviet squad, the only loss by the Soviets on their tour. This caught the attention of the owners of the OHL major junior Ottawa 67's and they soon offered him a coaching job, replacing Leo Boivin at the start of the 1974–75 season. He would continue coaching the 67's until 1984, when he became an assistant coach with the defending Stanley Cup champions, New York Islanders of the NHL. However, after two seasons, he would return to coaching the 67's. Head coach of the Sarnia Sting, Dave McQueen played for Kilrea and says that Kilrea had his players over to his house at Christmas but when you were in his 'dog house' it was often tough to get out.
Except for a brief retirement for the 1994–95 season, Kilrea coached the 67's until the end of the 2008–09 season, and is also the General Manager of the club. He has won the Memorial Cup, emblematic of Canada's major junior championship, twice with the 67's (1984 and 1999) and is the winningest coach in junior hockey history – a task completed on January 17, 1997 with his 742nd win. On February 2, 2007, Brian Kilrea coached his 2000th game as head coach of the 67's.
Kilrea has also won the Matt Leyden Trophy as OHL Coach of the Year in 1980–81, 1981–82, 1995–96, 1996–97 and 2002–03. Kilrea was also honoured with the Bill Long Award in 1994, for distinguished service to the OHL.
In 2003, Brian Kilrea was inducted into the Hockey Hall of Fame in the Builders category. The Brian Kilrea Coach of the Year Award, given annually to the top coach in the Canadian Hockey League, was renamed in his honour shortly after his induction into the Hockey Hall of Fame. Kilrea won the award in 1996–97 when it was known as the CHL Coach of the Year Award.
In twenty-nine seasons with the 67's he has only had six losing seasons – an extraordinary task in junior hockey, which due to age restrictions has a high turnover rate of players.
On September 3, 2008, Kilrea announced that 2008–09 would be his final season as coach of the 67's, though he plans to continue serving as general manager of the club.
On March 15, 2009, Ottawa beat the Kingston Frontenacs 5–3 to give Kilrea a win in his final regular season game, giving him 1,193 wins all-time.
Kilera returned behind the bench on October 17, 2014 for the Ottawa 67's to celebrate his 80th birthday. He became the oldest coach in hockey history, winning career game number 1,194 by a score of 6-3 against the Mississauga Steelheads.
Kilrea is a nephew of former NHL players Wally, Ken, and Hec Kilrea.
Since 1976, Kilrea has co-owned a restaurant with Nick Bouris called Chances R in Ottawa's west end. He is an honorary member of the Rideau View Country Club, a golf club located in Manotick, Ontario.
Kilrea suffered a heart attack on August 12, 2012, and subsequently underwent triple bypass surgery.
Note: GP = Games played, W = Wins, L = Losses, T = Ties, Pts = Points, GF = Goals for, GA = Goals against, PIM = Penalties in minutes