He was born in Penetanguishene, Ontario, Canada and started singing and playing drums at age 5. By his mid-teens, LaBrie was a member of several bands as a singer and/or drummer, and in 1981, at age 18, he moved to Toronto to further his musical pursuits. He currently still resides in Toronto, with his wife Karen, daughter Chloe, and son Chance.

After stints with various bands, he became the vocalist for glam rock band Winter Rose, who released a self-titled album in 1987.

In 1991 he learned that a relatively unknown American progressive metal band called Dream Theater was in the market for a singer, so he sent down a tape and was quickly flown to New York for a full audition. The trial went well, and he was chosen ahead of 200 other hopefuls to fill the full-time vocalist position in that band.

Having two Johns (Myung and Petrucci)in the band was confusing enough, so with another Kevin in the band already, LaBrie dropped his first name and adopted the stage name James LaBrie.

During the recording of Dream Theater's first album with LaBrie in the band, Images and Words, he didn't have much input into the musical composition, because the majority of the music was already written while the band was auditioning singers. He did however manage to exert some influence on the vocal melodies, which he devised with drummer Mike Portnoy and guitarist John Petrucci.

In 1993, he was one of the candidates to replace departed Iron Maiden vocalist, Bruce Dickinson. He has since had a significant impact on the vocal melodies on each Dream Theater album, but continues to have little input into the musical side of Dream Theater. To date he has written lyrics for at least one song on each album (excluding Images and Words) Dream Theater has released with him in the band.

In 1994, while vacationing in Cuba, LaBrie had severe food poisoning and while vomiting, ruptured his vocal cords. Two weeks later (and against doctor's orders) he had to go on tour again, with his voice not strong and cracking frequently. He went to several specialists who said the damage would take a while to heal. James also had surgery before going on tour. He finally started to get his voice back in 2002 and returned to just about full power in 2005. Many critics unaware of this event have given him much criticism on live albums such as Once in a Livetime and Live Scenes From New York.

His musical inspiration comes from many different genres, including such artists as Metallica, Ludwig van Beethoven, Nat King Cole, Queen and Sting, whose inspiration, according to LaBrie, is shown on Dream Theater's album "Octavarium", which was released on June 7, 2005.

Throughout his career with Dream Theater, he has lent his voice to many other artists' records as well as tribute albums to some influential artists. He has appeared on many Trent Gardner releases (including Leonardo: The Absolute Man and Explorer's Club), as well as appearing on albums by such artists as Ayreon (The Human Equation, released 2004), Shadow Gallery, Tim Donohue and Frameshift.

With Matt Guillory and Mike Mangini, LaBrie has released three solo albums under various names (Mullmuzzler, James LaBrie's Mullmuzzler, and simply James LaBrie). His latest, Elements of Persuasion, was released in March, 2005. A fourth solo album is widely rumored, amongst LaBrie's internet fanbase, to be in the works for a mid-late 2006 release. LaBrie has a studio vocal range of at about three octaves, though the fact that since his vocal recovery he has been able to hit the high and low notes with full force suggests that his actual range might be considerably larger.