Filming for the series took place in the United Kingdom, at Swansea, Neath, Port Talbot and Margam Castle in Wales. A 265,000-square-foot (24,600 m) studio in Swansea Gate Business Park was also used and several sets were built to resemble 15th-century Florence. Annie Symons was brought on board as the lead costume designer. Bear McCreary composed the score for the series, and orchestrated the main theme to reflect Leonardo's use of mirror writing. Goyer had a scene in episode five depicting a kiss between Leonardo and Jacopo Saltarelli filmed in secret as he feared network interference.
Da Vinci's Demons received three nominations for Outstanding Main Title Design, Outstanding Main Title Theme Music and Outstanding Special Visual Effects at the 65th Primetime Creative Arts Emmy Awards. The series won Main Title Design and Main Title Theme Music, but lost Visual Effects to the Cinemax series Banshee.
The series premiered in the United States on Starz on April 12, 2013, and its second season premiered on March 22, 2014. The series was renewed for a third season, which premiered on October 24, 2015. On July 23, 2015, Starz announced that the third season would be the show's last. However Goyer has left it open for a miniseries return.
Lead actor Tom Riley won best actor for his role as Leonardo da Vinci at the 2014 Bafta Cymru awards, where the show was also nominated for best production design and best costume design.