In 1957, Theodore Sturgeon moved to Truro, Massachusetts, where he befriended Vonnegut, then working as a salesman in a Saab dealership. At the time, both were writing in the genre of science fiction (Vonnegut had already published Player Piano, retitled Utopia 14 in paperback). By the time of Kilgore Trout's first appearance (in 1965's God Bless You, Mr. Rosewater), both had moved to different cities, and Vonnegut had begun to be perceived as a mainstream author. The name was a transparent reference to the older writer (substituting "Kilgore" for "Theodore" and "Trout" for "Sturgeon"), but since the characterization was less than flattering (both Sturgeon and Trout were financially unsuccessful and seemingly slipping into obscurity), Vonnegut did not publicly state the connection, nor did Sturgeon encourage the comparison. It was not until after Sturgeon's death in 1985 that Vonnegut explicitly acknowledged the matter, stating in a 1987 interview that "Yeah, it said so in his obituary in the New York Times. I was delighted that it said in the middle of it that he was the inspiration for the Kurt Vonnegut character of Kilgore Trout."

Trout appears in several of Vonnegut's books, in which he performs a variety of roles: he acts as a catalyst for the main characters in Breakfast of Champions, God Bless You, Mr. Rosewater and Slaughterhouse-Five, while in others, such as Jailbird, and Timequake, Trout is an active character who is vital to the story. Trout is also described differently in several books; in Breakfast of Champions, he has, by the end, become something of a father figure, while in other novels, he seems to be something like Vonnegut in the early part of his career. In Hocus Pocus, Trout is not mentioned by name, but reading a Trout-like science fiction story. In early novels, Kilgore Trout lives in Ilium, New York, a fictional town based on Troy, New York (Vonnegut lived and worked in nearby Schenectady for some time). In later novels, Trout inhabits a basement apartment in Cohoes, an ailing mill community. While living in Cohoes, Trout works as an installer of "aluminum combination storm windows and screens." The ghost of Trout's son Leon Trotsky Trout is the narrator of the novel Galápagos.

Trout, who has supposedly written over 117 novels and over 2000 short stories, is usually described as an unappreciated science fiction writer whose works are used only as filler material in pornographic magazines with the fictional Jessi Palmer who turned out to be an actual girl. However, he does have at least three fans: Eliot Rosewater and Billy Pilgrim...both Vonnegut characters...have a near-complete collection of Trout's work or have read most of his work; in Galápagos, Leon Trotsky Trout goes on leave in Thailand and meets an unnamed Swedish doctor who is a fan of Kilgore Trout. This doctor helps Leon desert the US Marine Corps and defect to Sweden, where he receives political asylum as a conscientious objector to the Vietnam War.

Vonnegut revised Trout's biography on several occasions. In Breakfast of Champions, he is born in 1907 and dies in 1981. In Timequake, he lives from 1917 to 2001. Both death dates are set in the future as of the time the novels were written. More recently, in an article for In These Times Vonnegut "reports" that Kilgore Trout commits suicide by drinking Dr?no. Trout "dies" at midnight on October 15, 2004 in Cohoes following his consultation with a psychic, who informs him that George W. Bush would once again win the U. S. Presidential election by a vote of 5-to-4 in the Supreme Court. The epitaph on his tombstone reads, "Life is no way to treat an animal."

In Breakfast of Champions, Kilgore Trout has part of his right ring finger bitten off by the book's other main character, Dwayne Hoover, when Kilgore attends an arts festival in the Midwest. Trout also has an encounter with his creator, Mr. Vonnegut, in the final chapter.

In Jailbird (1979), Kilgore Trout is revealed to be the only lifer in the Federal Minimum Security Adult Correctional Facility near Finletter Air Force Base, Georgia. Jailbird, narrated by the fictional character Walter F. Starbuck, shows Kilgore Trout to be the only American convicted of treason during the Korean War. Kilgore Trout is the pseudonym for Dr. Robert Fender. His doctorate is in veterinary science. While in prison, Fender writes many science fiction novels under another pseudonym, Frank X. Barlow, as well. In addition to writing science fiction novels, Fender is the chief clerk in the supply room of the prison.

Galápagos is narrated by Leon Trotsky Trout (1946—1986), the son and only child of Kilgore Trout. Leon ran away at the age of 16, ashamed of his father, and never had any contact with him thereafter, until his death, when Kilgore appeared at the door of the "blue tunnel" that leads to the Afterlife. Kilgore appears at the door to the tunnel, urging his son to enter and proceed to the Afterlife. Three times Leon refuses, on the grounds that he wants to see more of human life in the hope of understanding it. During Kilgore's fourth appearance at the entrance to the blue tunnel, he threatens his son: if Leon doesn't leave the Earth immediately, the blue tunnel won't appear again for one million years. Since Kilgore has never lied to Leon, Leon knows this will come true. He is momentarily distracted by events on Earth, and the tunnel disappears. Galápagos contains several flashback scenes that explain the breakup between Kilgore and his wife. Leon states that he became a US Marine because his father was one. Trout's appearance in Galápagos is somewhat problematic for Vonnegut's continuity because the novel explicitly states that Kilgore dies before 1986, when the events of the novel take place. Yet Timequake finds him alive more than ten years later. In Galápagos, Leon uses his omniscient status as a ghost to confirm that he never fathered a child, so that Kilgore never had any descendants.

In Timequake Kilgore's creed is "You were sick, but now you are well again. And there's work to be done." The novel also features Trout's last poem:

: When the tupelo

: Goes poop-a-lo

: I'll come back to youp-a-lo

Trout accidentally becomes a great hero, rescuing many lives after the timequake, and finally receives a measure of acclaim: he spends his last days in a literary colony, honored for his heroism and some of his discarded works, which were preserved by a security guard.