Karen Kain's mother enrolled her daughter in ballet training because she believed it would improve her posture, poise, and discipline. At age 11, she began training at the National Ballet School of Canada. Upon graduating in 1969, she was invited to join the National Ballet of Canada.
Kain became a principal dancer in 1971, performing central roles in a wide array of ballets, eventually becoming well known in Canada, with the help of legendary dancer Rudolf Nureyev. She worked as a guest artist with Roland Petit's Ballet National de Marseilles, the Bolshoi Ballet, the London Festival Ballet, the Paris Opera Ballet, the Hamburg Ballet, the Vienna State Opera Ballet, and the Eliot Feld Ballet.
In 1977, Kain stopped dancing, but started again in 1981 with the National Ballet of Canada, where she performed for 15 more years. In 1998, she returned to the National Ballet of Canada as part of the senior management team, in the role of artistic associate. In 2005, she succeeded James Kudelka as artistic director.