TF1 initially commissioned a pilot of two episodes before extending the first season with four additional episodes.

Hélène de Fougerolles announced on social media in December 2020 that she was leaving the series after season 3. She later explained in a February 2021 interview with Télé-Loisirs that the departure was not entirely her choice, as writers wanted to shake things up once the two lead characters got together, and since the show is named 'Balthazar', it made more sense to renew Tomer Sisley's character rather than hers.

Filming for the second season began on 18 February 2019, with lead actor Tomer Sisley directing the fifth episode himself.

Filming for the fifth and final season began on 15 March 2022, according to actress Constance Labbé.

During a February 2022 appearance on '50 minutes inside', Tomer Sisley suggested the upcoming fifth season would be the last, but days later on Sud Radio he walked back the statement, saying it was uncertain whether a sixth season might follow. TF1 ultimately confirmed on 4 December 2022 that the series would end after season 5.

A critic for the Belgian magazine Moustique compared the duo of Raphaël Balthazar and Hélène Bach to Patrick Jane and Teresa Lisbon from the American series The Mentalist.

Since 2018, Balthazar has been TF1's most profitable and highest-rated series, ranking as the third most-watched program in France in 2019 with an average of 6.8 million viewers, and second in 2020 behind Capitaine Marleau.

The show was one of the ten highest-rated dramas in France in 2018, finishing twelfth among the most-watched series that year, behind Joséphine, ange gardien.