She began her career in television, appearing in the miniseries Anne of Green Gables (1985) before having a recurring role on the Canadian series The Campbells (1986–1990).

Lyon continued to appear on television throughout the 1990s, including providing the voice of Queen Serenity in the animated series Sailor Moon (1995).

She returned to film with a minor role in the drama Focus (2001), starring William H. Macy and Laura Dern, followed by the independent comedy Childstar (2004).

Lyon had a minor role in the psychological thriller Regression (2015) before appearing in Guillermo del Toro's critically acclaimed fantasy film The Shape of Water (2017).

In 2019, Lyon had a multi-episode arc on the American political thriller series Designated Survivor, starring Kiefer Sutherland.