Many scientists, including Albert Einstein and Nikola Tesla, have contributed articles to it, with more than 150 Nobel Prize-winners being featured since its inception.

It also reported on a broad range of inventions including perpetual motion machines, an 1860 device for buoying vessels by Abraham Lincoln, and the universal joint which now can be found in nearly every automobile manufactured.

Current issues include a "this date in history" section, featuring excerpts from articles originally published 50, 100, and 150 years earlier.

[13] Offices of the Scientific American have included 37 Park Row in Manhattan and the Woolworth Building in 1915 when it was just finished two years earlier in 1913.

[3] Scientific American published its first foreign-language edition in 1890 in Spanish, titled La América Científica é Industrial, but ended sometime in the early 1900s.

[17] In 2013, Danielle N. Lee, a female scientist who blogged at Scientific American, was called a "whore" in an email by an editor at the science website Biology Online after refusing to write professional content without compensation.

[38] These editions are typically released quarterly and cover themes such as space settlement by humans, evolution, economics, and climate change.

The magazine’s archive provides a comprehensive list of past issues, including special editions, dating back to its inception in 1845.

In March 1996, Scientific American launched its own website that included articles from current and past issues, online-only features, daily news, special reports, and trivia, among other things.

Topics covered dozens of areas of scientific knowledge and included in-depth essays on: The Animal Mind; Atmosphere, Climate, and Change; Beyond the Third Dimension; Cosmic Clouds; Cycles of Life • Civilization and the Biosphere; The Discovery of Subatomic Particles; Diversity and the Tropical Rain Forest; Earthquakes and Geological Discovery; Exploring Planetary Worlds; Gravity's Fatal Attraction; Fire; Fossils and the History of Life; From Quarks to the Cosmos; A Guided Tour of the Living Cell; Human Diversity; Perception; The Solar System; Sun and Earth; The Science of Words (Linguistics); The Science of Musical Sound; The Second Law (of Thermodynamics); Stars; Supercomputing and the Transformation of Science.

[46] In April 1950, the U.S. Atomic Energy Commission ordered Scientific American to cease publication of an issue containing an article by Hans Bethe that appeared to reveal classified information about the thermonuclear hydrogen bomb.

[48] In the October 2020 issue of the magazine, it endorsed Joe Biden for the 2020 presidential election, citing Donald Trump's rejection of scientific evidence, especially during the COVID-19 pandemic in the United States.

"[51] In September 2024 and for the second time in its history, for the same reason, Scientific American endorsed Kamala Harris for the 2024 United States presidential election.

[52] In November 2024 editor-in-chief Laura Helmuth resigned from Scientific American following an apology for a social media post in which she characterized some supporting Trump as fascists.