Jack Bush began his career as a professional illustrator, starting at the age of 19 when he worked for Rapid Grip in Toronto, and he spent 40 years in this career. From 1942 to 1959 he ran his own company Wookey, Bush and Winter, and won numerous awards for his work in this field. In the early days, he attended night classes at the Ontario College of Art, taking instruction from teachers such as Charles Comfort and J.W. Beatty while pursuing painting in his free time. Before World War II, Bush's subjects were landscapes and townscapes. He involved himself in various art organizations - the Canadian Society of Painters in Water Colour, the Canadian Group of Painters, which carried on the legacy of the Group of Seven and the Royal Academy of Arts.

From 1945 to 1947, the post-war years brought the influence of Social Realism into his work, and the angst present in this work was radiating from his psyche. Bush reached out to psychiatrist Dr. Allan Walters, who encouraged a more spontaneous approach to expressing his feelings in his art, and to keep a diary, which he did for the last 25 years of his life. This was a powerful catalyst for change in Bush's work. In 1950 he traveled to New York, spending time in galleries such as the Museum of Modern Art. He was energized and excited by the contemporary abstract art he saw, and by the mid-1950s, abstraction would dominate his work. In 1953, he participated in the formation of Painters Eleven in Toronto, which provided an outlet for the members to exhibit their abstract work. In another pivotal moment, Bush met influential American art critic Clement Greenberg in 1957, and Greenberg's critiques and their conversations had an important effect on his work.

By 1961 Bush was entering his mature period of abstraction, and he was exploring his ideas in series, such as the Thrust and Flag paintings of the early 1960s. The period from 1963 to 1968 was known as the Apollonian phase, and generated works with bold forms and stunning colour in series such as the Fishtails, Sashes, Stacks and Fringes. In the 1970s came Series D, then the Totems (1973 to 1974), then a few years later the Handkerchief series. Bush also loved the ballet and jazz, and references to movement and music were sometimes woven into his work.

Bush is recognized as one of Canada's foremost modernist painters, and he received international recognition, particularly after 1960, when he established a market for his work in New York with André Emmerich Gallery, in Los Angeles with Nicholas Wilder Gallery and in London at Waddington Galleries. In 1967, along with Jacques Hurtubise, he represented Canada in the São Paulo IX Biennial. In 1976, a retrospective of his work was held at the Art Gallery of Ontario, which traveled across the country, and in 2014 a major retrospective was held at the National Gallery of Canada.