The series is based on the ABC News podcast of the same name, hosted by Rebecca Jarvis, who also served as an executive producer.

The Dropout is the first television project produced by Searchlight Television.

Kate McKinnon was originally cast to play Elizabeth Holmes but dropped out of the project on February 18, 2021, without providing an explanation.

Amanda Seyfried was cast to replace Kate McKinnon as Elizabeth Holmes on March 29, 2021, and also joined the miniseries as a producer.

The character Rakesh Madhava, a Theranos engineer played by Utkarsh Ambudkar, is entirely fictional.

The character Brendan Morris, an engineer played by Bashir Salahuddin, is fictional and is closest in inspiration to real-life Theranos employee Tony Nugent.

The character Judith Baker, played by LisaGay Hamilton, is loosely based on John Carreyrou's real-life editor at The Wall Street Journal, Gerard Baker.

Michael Showalter, who joined as executive producer in March 2021, directed the first four episodes of the series.

Amanda Seyfried won the Primetime Emmy Award for Outstanding Lead Actress and the Golden Globe for Best Actress for her portrayal of Elizabeth Holmes.