Eisenberg was born in New York City in 1919 to Sidney Eisenberg, a furniture salesman, and Yetta Yellen, and grew up in the Bronx during the Great Depression. Eisenberg attended City College of New York before going to Polytechnic Institute of Brooklyn, where he received his Ph.D. in Electronics. After serving as a radar operator in the Air Force during World War II, Eisenberg married Frances Brenner in 1950. They have one daughter and one son.
Eisenberg was for many years a biomedical engineer at Rockefeller University, where he and Dr. Robert Schoenfeld were co-heads of the Electronic Lab. He designed the first transistorized radio-frequency coupled pacemaker in about 1960 in collaboration with Dr. Alexander Mauro. It is currently on display at Caspary Hall, Rockefeller University.
Eisenberg published his first short story, "Dr. Beltzov's Polyunsaturated Kasha Oil Diet," in Harper's Magazine in 1962. His first science fiction publication was later that year with his story "The Mynah Matter" in the August 1962 Fantastic Stories of Imagination, with Eisenberg debuting alongside fellow author Roger Zelazny.
Shortly after that, Eisenberg began publishing his stories in many of the leading science fiction magazines of the day, including The Magazine of Fantasy and Science Fiction, Galaxy Science Fiction, and If. Eisenberg's science fiction takes a humorous approach to storytelling. As Eisenberg has said, "I enjoy wedding humor with science fiction, particularly where some unsavory aspect of our society can be pricked."
Many of Eisenberg's stories feature his character Professor Emmet Duckworth, a research scientist and two-time winner of the Nobel Prize. Duckworth's "bright ideas seem great at first but always end in disaster" with one of the professor's many inventions being "an addictive aphrodisiac clocking in at 150,000 calories per ounce—along with a propensity to turn those taking it into walking bombs." A number of the Duckworth stories were collected in Eisenberg's short story collection The Best Laid Schemes, published in 1971 by MacMillan.
Eisenberg is best known for his short story What Happened to Auguste Clarot?, which was published in the anthology Dangerous Visions edited by Harlan Ellison. His stories have also been reprinted in anthologies such as Great Science Fiction of the 20th Century, The 10th Annual of the Year’s Best SF, and Great Science Fiction By the World's Great Scientists.
He has published two books of limericks (both with George Gordon), and one collection of short stories, Best Laid Schemes. More recently, he has gained a cult following for the limericks he posts in the comments sections of various New York Times articles and has been called the "closest thing this paper has to a poet in residence."
Eisenberg wrote the following limerick about his life
A nonagenarian, I,
A sometime writer of sci-fi,
Gen’rally of good cheer,
From a New York Times reader: "The Eisenberg Certainty Principle":
There once was a poet named Larry
Whose thoughts one could never quite parry
For when Larry had spoken
The mold it was broken
Though the topics invariably vary.