Knight's first professional sale was a cartoon drawing to a science-fiction magazine, Amazing Stories. His first story, "Resilience", was published in 1941: an editorial error made this story's ending incomprehensible, although the story was later reprinted elsewhere as Knight originally wrote it. He was a recipient of the Hugo Award, founder of the Science Fiction and Fantasy Writers of America (SFWA), cofounder of the National Fantasy Fan Federation, cofounder of the Milford Writer's Workshop, and cofounder of the Clarion Writers Workshop. Knight lived in Eugene, Oregon, with his wife Kate Wilhelm, also a science fiction writer.

At the time of his first story, he was living in New York, and was a member of the Futurians. One of his short stories describes paranormal disruption of a science fiction fan group, and contains cameo appearances of various Futurians under thinly-disguised names: for instance, H. Beam Piper is identified as "H. Dreyne Fifer".

In a series of reviews for various magazines, he became famous as a science fiction critic, a career which began when he wrote in 1945 that A. E. van Vogt "is not a giant as often maintained. He's only a pygmy using a giant typewriter." After nine years, he ceased reviewing when a magazine refused to publish one review exactly as he wrote it. These reviews were later collected in In Search of Wonder.

Damon worked as an editor for Chilton Books in 1965. He read Dune World in Analog magazine and was responsible for tracking down Frank Herbert to publish Dune. Twenty other publishing companies had turned it down before the Chilton offer. Ironically this brilliant insight probably led to his dismissal from Chilton a year later because of high publication cost and poor initial book sales.

The SFWA's Damon Knight Memorial Grand Master Award for lifetime achievement was renamed in his honor. Formerly known as the Grand Master Award, Knight received that honor in 1994.

To the general public, he is best known as the author of "To Serve Man", which was adapted for The Twilight Zone. He is also known for the term "second-order idiot plot," a story that only functions because almost everyone in it is an idiot.

One of Knight's best-known stories, "The Country of the Kind" (reprinted in The Science Fiction Hall of Fame, Volume One) describes a future utopia in which everyone is peaceful, kindly and honest ... except for a single individual who is compelled to be destructive and abusive; his mental illness (and artistic temperament) is contrasted with savage irony to their bland but apparently contented conformity. Another particularly interesting piece is "Rule Golden", in which an alien spreads a chemical that makes everyone receive as much pain as they give unto others. The consequences of what this would do to governments in general, and America's role in the world, are discussed in some detail.

Novels

• Hell's Pavement (1955)
• VOR (with James Blish) (1958)
• A for Anything (1st Edition titled "The People Maker") (1959)
• Masters of Evolution (1959)
• The Sun Saboteurs (1961)
• Beyond the Barrier (1964)
• Mind Switch (1965)
• Off Centre (1965)
• The Rithian Terror (1965)
• The Earth Quarter (1970)
• World without Children (1970)
• The World and Thorinn (1980)
• The Man in the Tree (1984)
• CV (1985)
• The Observers (1988)
• Double Meaning (1991)
• God's Nose (1991)
• Why Do Birds (1992)
• Humpty Dumpty: An Oval (1996)

Short stories and other writings

• "Not with a Bang" (1949)
• "To Serve Man" (1950)
• "Ask Me Anything" (1951)
• "Cabin Boy" (1951)
• "Natural State" (1951)
• "The Analogues" (1952)
• "Beachcomber" (1952)
• "Ticket to Anywhere" (1952)
• "Anachron" (1953)
• "Babel II" (1953)
• "Four in One" (1953)
• "Special Delivery" (1953)
• "Rule Golden" (1954)
• "The Country of the Kind" (1955)
• "Dulcie and Decorum" (1955)
• "You're Another" (1955)
• "Extempore" (1956)
• "The Last Word" (1956)
• "Stranger Station" (1956)
• "The Dying Man" (1957)
• "The Enemy" (1958)
• "An Eye for a What?" (1957)
• "Be My Guest" (1958)
• "Eripmav" (1958)
• "Idiot Stick" (1958)
• "Thing of Beauty" (1958)
• "The Handler" (1960)
• "Time Enough" (1960)
• A Century of Science Fiction (1962) (editor)
• The Big Pat Boom (1963)
• God's Nose (1964)
• Maid to Measure (1964)
• "Shall the Dust Praise Thee?" (1967)
• Masks (1968)
• I See You (1976)
• The Futurians (1977, memoir/history)
• Creating Short Fiction (1981) (advice on writing short stories)
• Forever (1981)
• O (1983)
• Strangers on Paradise (1986)
• Not a Creature (1993)
• Fortyday (1994)
• Life Edit (1996)
• Double Meaning
• In the Beginning
• In Search of Wonder (1956) (collected reviews and critical pieces)
• Turning Points (editor/contributor: critical anthology)
• Orbit (editor)
• "The Big Pat Boom" appears in "The Seventh Galaxy Reader" (ed by Frederik Pohl)