As a child, Moskowitz greatly enjoyed reading science fiction pulp magazines. As a teenager, he organized a branch of the Science Fiction League. Meanwhile, Donald A. Wollheim helped organize the Futurians, a rival club with Marxist sympathies. While still in his teens, Moskowitz became chairman of the first World Science Fiction Convention held in New York City in 1939. He barred several Futurians from the convention because they threatened to disrupt it. This event is referred to by historians of fandom as the "Great Exclusion Act".
Moskowitz later worked professionally in the science fiction field. He edited Science-Fiction Plus, a short-lived genre magazine owned by Hugo Gernsback, in 1953. He compiled about two dozen anthologies, and a few single-author collections, most published in the 1960s and early 1970s. Moskowitz also wrote a handful of short stories (three published in 1941, one in 1953, three in 1956). His most enduring work is likely to be his writing on the history of science fiction, in particular two collections of short author biographies, Explorers of the Infinite and Seekers of Tomorrow, as well as the highly regarded Under the Moons of Mars: A History and Anthology of "The Scientific Romance" in the Munsey Magazines, 1912–1920. His exhaustive cataloging of early sf magazine stories by important genre authors remains the best resource for nonspecialists.
Theodore Sturgeon, although noting the book's many imperfections, praised Explorers of the Infinite, saying "no one has surveyed the roots of SF as well as Mr. M.; probably no one ever will; prossibly [sic], no one else can."
Reviewing Seekers of Tomorrow, Algis Budrys wryly noted that "Moskowitz is a master of denotation. He wouldn't know a connotation if it snapped at his ankle, which is something that happens quite often." He added, however, that "Moskowitz knows and transmits, at least as much about the history of science fiction and its evolution, as anyone possibly could."
Moskowitz's works include also The Immortal Storm, a historical review of internecine strife within fandom. Moskowitz wrote it in a bombastic style that made the events he described seem so important that, as fan historian Harry Warner Jr. quipped, "If read directly after a history of World War II, it does not seem like an anticlimax." Floyd C. Gale wrote in his review of the book that "[f]ortunately, most of these petulant warriors have since grown up—but their historian is still leading their ghostly legions that are more real than today to him. The miracle is that S-F survived even the love of its most rabid fans". Anthony Boucher noted that "never has so much been written about so little," but added that the book was "a unique document not without a good deal of social and psychological value."
Moskowitz was also renowned as a science fiction book collector, with a tremendous number of important early works and rarities. His book collection was auctioned off after his death.
As "Sam Martin", he was also editor of the trade publications Quick Frozen Foods and Quick Frozen Foods International for many years.
First Fandom, an organization of science fiction fans active before 1940, gives an award in Moskowitz' memory each year at the World Science Fiction Convention.
Moskowitz smoked cigarettes frequently throughout his adult life. A few years before his death, throat cancer required the surgical removal of his larynx. He continued to speak at science fiction conventions, using an electronic voice-box held against his throat. Throughout his later years, although his controversial opinions were often disputed by others, he was recognized as a leading authority on the history of science fiction.