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 A History and Anthology of “The Scientific Romance” in the Munsey Magazines, 1912-1920. Moskowitz has been criticized for eccentrically assigning priorities and tracing influences regarding particular themes and ideas based principally on publication dates, as well as for some supposed inaccuracies. His exhaustive cataloguing of early sf magazine stories by important genre authors remains the best resource for nonspecialists.

Moskowitz's most popular work may be 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."

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 indisputably recognized as the leading authority on the history of science fiction.