The show features discussions of recent scientific developments in layman's terms, and interviews authors, people in the area of science, and other famous skeptics.

The SGU podcast includes discussions of myths, conspiracy theories, pseudoscience, the paranormal, and other forms of superstition, from the point of view of scientific skepticism.

[3] In 2018 Jay Novella, who had previously both been one of the cast and managed the podcast's website, was employed full-time as a result of reaching a Patreon target of 3,000 donors.

[3] Segments include interviews, discussions of significant but largely unknown figures in science, short games and puzzles played with the audience or between the panellists, and accounts of relevant events in the news that relate to skepticism.

The addition of sponsors is not permanent, according to Novella, they shall be removed "if 4% of listeners support the SGU through membership at an average of the $8 per month level.

Membership entitles one to an ad-free version of The SGU, extra content, and discounts to NECSS (The Northeast Conference on Science and Skepticism).

[1] These live shows may be located on the most complete and accurate reproduction of the Starship Enterprise Star Trek: The Original Series set, which was built by James Cawley and can be seen on the SGU Patreon page introduction video.

In an interview with The European Skeptics Podcast, Jay Novella describes their approach to writing the book from the "point of view of an alien species observing the earth from a skeptical perspective using critical thinking," reminiscent of the podcast's namesake The Hitchhiker's Guide to the Galaxy by Douglas Adams.