During the 60s and 70s Blake taught widely and also exhibited his work in many individual and group shows, both domestically and internationally. In 1961 he won the John Moores Award for his work Self-Portrait with Badges, and was also featured in Ken Russell's BBC film on Pop Art 'Pop Goes the Easel', which first brought him to wide popular attention. In 1969 Blake left London to live in the West Country where he was a founding member of the Brotherhood of Ruralists. He continued to live near Bristol until 1979; during this period his work moved away from the glossy commercial pop art for which he is most celebrated and focused instead on literary and rural subjects.

Blake moved back to Chiswick in 1979; upon his return to London his work reverted to his earlier pop culture references. He was elected a member of the Royal Academy of Arts in 1981 and appointed a CBE in 1983. A major retrospective of his work - "Now We Are 64" - was held at the National Gallery in 1996, and another at Tate Liverpool in 2007.

Blake's work reflects his fascination with all streams of popular culture and the beauty to be found in everyday objects and surroundings. Many of his works feature found printed materials such as photographs, comic strips or advertising texts, combined with bold geometric patterns and the use of primary colours. The works perfectly capture the effervescent and optimistic ethos of the sixties, but are also strikingly fresh and contemporary. Blake is renowned for his connections with the music industry, having produced iconic album covers for the Beatles, Paul Weller, The Who, and Oasis.