Hamilton was born on March 24, 1916 in Uppsala, Sweden. He later emigrated to the United States, attended the University of Chicago (receiving a Bachelor of Science degree in 1938), and served in the United States Navy Reserve during World War II. He was married to Kathleen Hamilton (née Stick) from 1941 until her death in 1989. The couple had four children: Hugo, Elise, Gordon, and Victoria Hamilton.

A long-time resident of Santa Fe, New Mexico, Hamilton was a skilled outdoorsman and hunter who wrote non-fiction articles for outdoor magazines and published a book-length collection of them. For a number of years after leaving Santa Fe he lived on his own yacht, then relocated to Sweden where he resided until his death in 2006. A number of his Matt Helm novels are situated in the Santa Fe area and American Southwest in general; as Hamilton developed an interest in boating, many of the books began to have a nautical background as well.

Hamilton began his writing career in 1946, fiction magazines like Collier's Weekly and The Saturday Evening Post. His first novel Date With Darkness was published in 1947; over the next forty-six years he published a total of thirty-eight novels. His first three books were published in hardcover by Rinehart. After WWII American publishers began to experiment with issuing original paperback fiction. Most of his early novels whether suspense, spy, and western published between 1954 and 1960, were typical paperback originals of the era: fast-moving tales in paperbacks with lurid covers. The most interesting of them is, arguably, Murder, (alternate title: Assassins Have Starry Eyes), in which a mathematician working on the design for a nuclear bomb has to save his kidnapped wife from a group of shadowy villains. Several classic western movies, The Big Country and The Violent Men, were adapted from two of his western novels.

The Matt Helm series, published by Gold Medal which began with Death of a Citizen in 1960 and ran for 27 books, ending in 1993 with The Damagers, was more substantial. Helm, a wartime agent in a secret agency that specialized in the assassination of Nazis, is drawn back into a post-war world of espionage and assassination after fifteen years as a civilian. He narrates his adventures in a brisk, matter-of-fact tone with an occasional undertone of deadpan humor. He describes gunfights, knife fights, torture, and (off-stage) sexual conquests with a carefully maintained professional detachment, like a pathologist dictating an autopsy report or a police officer describing an investigation. Over the course of the series, this detachment comes to define Helm's character. He is a professional doing a job; the job is killing people. Hamilton completed one more Matt Helm novel, The Dominators in 2002, that hasn't been published.

The noted Golden Age mystery writer John Dickson Carr began reviewing books for Ellery Queen's Mystery Magazine in 1969, and often praised thrillers of the day. According to Carr's biographer, "Carr found Donald Hamilton's Matt Helm to be 'my favorite secret agent,'" although Hamilton's books had little in common with Carr's. "The explanation may lie in Carr's comment that in espionage novels he preferred Matt Helm's Cloud cuckoo land. Carr never valued realism in fiction."

General audiences may be more familiar with Matt Helm through a series of popular action-comedy films produced in the late 1960s starring Dean Martin in the title role. These films are only very loosely based upon Hamilton's writings. DreamWorks optioned the film rights to Hamilton's books in 2002 and began planning a more serious adaptation of the Matt Helm novels, but the project is in limbo.

Hamilton died in his sleep on November 20, 2006.

• John Dickson Carr, The Man Who Explained Miracles, by Douglas G. Greene, New York, 1995

• Encyclopedia of Mystery and Detection, by Chris Steinbrunner and Otto Penzler, New York, 1976, ISBN 0-07-061121-1