The series is inspired by the Oliver Sacks books The Man Who Mistook His Wife for a Hat and An Anthropologist on Mars, and protagonist Oliver Wolf is named after Oliver Wolf Sacks.

The project was originally in development at Fox starting in November 2019, but Fox ultimately did not move forward with it; development then moved to NBC in January 2023.

The show was originally titled Dr. Wolf before being renamed Brilliant Minds on May 1, 2024.

Production of the first season was pushed to the 2024–25 season due to delays caused by industry strikes.

Principal photography for the series takes place in Toronto, Canada, rather than its onscreen setting of New York City.

Guest star Eric Dane received widespread praise for playing a firefighter battling ALS in the season 2 episode "The Fire Fighter," marking his first acting role since he publicly announced his own ALS diagnosis in April 2025.

NBC pulled the second season from its schedule in February 2026, replacing it with two-hour episodes of The Voice, before canceling the series entirely on May 1, 2026 after two seasons.

Rotten Tomatoes gave the series an 88% approval rating based on 17 critic reviews, with critics praising Zachary Quinto's performance, while Metacritic scored it 64/100 based on 10 critics.