After coming back to Quebec City, Lepage wrote, directed and played in a few independent productions and joined Théâtre Repère in 1980.

Lepage was the artistic director of the National Arts Centre's Théâtre français in Ottawa from 1989 to 1993, and continued to stage plays.

Lepage and Ex Machina have toured a number of productions internationally to critical and popular acclaim, including The Seven Streams of the River Ota (1994) and Elsinore (1995).

Lepage has directed five other feature films: The Confessional (Le Confessionnal) (1995), Polygraph (Le Polygraphe) (1996), Nô (1998), Possible Worlds (2000) and Triptych (Triptyque) (2013) (the latter co-directed by Pedro Pires), and has acted in films by other directors, including Jesus of Montreal (Jésus de Montréal) (1989) and Stardom (2001) by Denys Arcand.

Finally, Cirque du Soleil asked him to create the permanent Las Vegas show named Kà at the MGM Grand in 2005.

Three scenes of Lipsynch were later adapted to create the installation FRAGMENTATION (2011) by Richard Castelli and Volker Kuchelmeister for the stereoscopic system ReACTOR, designed by Sarah Kenderdine and Jeffrey Shaw.

He also staged Igor Stravinsky's The Rake's Progress, which was presented in Brussels' Opéra de la Monnaie in April 2007 and San Francisco War Memorial Opera House in November 2007.

For forty nights, a forty-minute show was displayed by the banks of Bassin Louise, using the huge surface of the Bunge grain elevators as a giant screen.

[6] Lepage then wrote and directed Totem, Cirque du Soleil's next touring show,[7] and began work on a new production of Der Ring des Nibelungen by Richard Wagner for the Metropolitan Opera of New York.

[16][17] In 2012, Lepage appeared as a hologram in Martin Villeneuve's Mars et Avril, a science fiction film based on the graphic novels of the same name.

[23] In 2018, Lepage launched SLĀV at the Montreal Jazz Festival; Betty Bonifassi's creation was so controversial that it was cancelled due to public protest - with the charge that white people singing the songs of black 19th-century slaves constituted cultural appropriation.

[24][25] Lepage's next production, Kanata, planned for Paris in December 2018, presenting Europeans' first settlement of Canada, was cancelled in July, 2018, after complaints from members of the Indigenous community led to his financial backers' withdrawal.

[27] Lepage's production of Mozart's The Magic Flute was presented in Quebec in July and August 2018 and there are plans to bring it to the Metropolitan Opera.

[35] He was promoted to Companion of the Order of Canada in 2009 "for his international contributions to the performing arts, particularly in film, theatre and opera, as an actor, producer and director".

The choice of Lepage, like that of America's Robert Wilson in his time, has to be seen primarily in the context of a cultural policy which, as provided for in the rules of the Prize laid down in 1986 in agreement with the European Commission, has as its objective the presentation of prizes to "a theatre personality or institution that has contributed by the creation of cultural events of significance to mutual understanding and knowledge among nations".