The revival was driven partly by a surge in popularity of the original show after it became available on Netflix in 2016, along with successful revival projects like Fuller House.

Steven Spielberg attended every pitch meeting and insisted on maintaining most elements of the original show, including the original voice cast and orchestrated music, and pushed for more political satire in the new series.

The show's introductory short is a parody of Jurassic Park, featuring a caricature of Spielberg as John Hammond 'reanimating' the Warners, partly inspired by wanting to recreate the same generational effect as Jurassic World had with Jurassic Park.

Classic characters like Hello Nurse and Thaddeus Plotz were deliberately left out of the revival due to changing sensibilities between the 1990s and 2020s, with Plotz replaced by a new Latina-American CEO named Nora Rita Norita.

The producers attempted to include a segment featuring Freakazoid, but it fell through due to actor availability.

Original series creator Tom Ruegger was not asked upfront to help craft the revival; he was later offered the chance to submit a script but declined, feeling it would be like auditioning for a show he created.

Original series writer and voice actress Sherri Stoner returned in 2023 to voice Slappy Squirrel for the revival's final episode.

The show's new character look was developed by artist Genevieve Tsai, who studied the TMS Entertainment-animated episodes of the original series (considered the best-looking) as well as older Looney Tunes shorts to create a more angular design for the Warners.

Composers Steven and Julie Bernstein scored the revival with a 35-piece orchestra, recording remotely with musicians in separate locations due to the COVID-19 pandemic lockdown.

Episodes were written in 2019 anticipating events of 2020, such as the Summer Olympics, but the COVID-19 pandemic disrupted some of these planned references.

The show's first episode caused controversy over a background joke referencing Johnny Depp in a poster parody titled 'Telling Lies,' which aired shortly after Depp lost his lawsuit against The Sun; Rob Paulsen clarified the episode was animated before the Depp-Heard-Sun legal battle began and the joke only referenced the nursery rhyme.

Tom Ruegger publicly criticized the reboot, calling it 'morally, ethically and professionally wrong' for not bringing back the original creative team and for using the Animaniacs title despite excluding many of the original supporting characters.