The annual honour is given to a person deemed to have made a significant contribution to the state of literature in Canada.
The Guelph, Ontario-based writer and artist will become the first graphic novelist to win the award. He will receive the accolade on October 29, the final night of the International Festival of Authors at Toronto's Harbourfront Centre.
Seth said in a statement: "I was bowled over when I heard I was to be awarded the 2011 Harbourfront Festival Prize.
"I recall back in the early '90s talking to fellow cartoonist Chester Brown about the future of our medium and our hopes of its literary acceptance. We weren't optimistic.
"Frankly, the idea of winning something like this was not within the realm of possibilities at that time so it goes without saying, that I am deeply honoured."
The Palookaville, Wimbledon Green and It's a Good Life if You Don't Weaken creator - born Gregory Gallant - has previously been honoured at the Eisner, Harvey and Ignatz Awards.
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