The first season was filmed on soundstages at Atlantic Studios Cooperative Sound Stage in Corner Brook, while seasons two through four moved production to Toronto.

A spin-off television film titled Vacation with Derek was filmed in northern Ontario in fall 2009 and aired on Family Channel on June 25, 2010.

On May 12, 2020, Shaftesbury Films announced a spinoff television film titled Life with Luca, set 15 years after the original series, which premiered in February 2023.

Actors Jordan Todosey and Daniel Magder, who played Lizzie and Edwin, did not return for the spinoff film Life with Luca; WildBrain Television cited 'scheduling challenges', though Todosey claimed she was never contacted.

Sarah Gadon played the recurring character Victoria in the first season episode 'The Wedding', with the role later recast to Paula Brancati for a season 4 episode.

Life with Derek and another Canadian sitcom, Naturally, Sadie, were both added to Disney Channel in the United States in 2005; while Naturally, Sadie was pulled in 2007, Life with Derek remained on the channel until January 2010.

The show won the 2009 Gemini Award for Best Children's or Youth Fiction Program or Series, and Michael Seater won Best Performance in a Children's or Youth Program or Series the same year.

In the film Life with Luca, several former recurring characters are given updated fates, including Principal Frank Lassiter becoming a Customs and Border Protection officer and Ralph Papadapolis becoming a brain surgeon.