The character's potential existence was first referenced in the press in February 2009 when Michael Ausiello hinted at the possibility of Meredith having a half-sibling, the product of her mother's affair with Richard. Initial speculation pointed to Jesse Williams' Jackson Avery as the child, but the actor refuted those rumors. Shonda Rhimes revealed that the character had always been a part of the original story plans, but the character's existence was not set in stone until season 4.

On April 5, 2014, TVLine reported that Kelly McCreary best known for her series regular role on The CW's short lived medical drama Emily Owens, M.D. and recent guest appearances on Scandal had been cast in a guest star role. McCeary was slated to debut on the May 8, 2015 episode. On October 23, 2014, it was announced that McCreary was promoted to series regular after being credited as guest-starring until the eleventh episode. It was a couple of months after McCreary wrapped her stint on Scandal that she was invited to audition for Grey's. McCeary revealed that she originally auditioned for the character of "Claudette" with dummy sides, unbeknownst to her. The only information McCeary had about the character was "that she was adopted, that she would recur, and she was going to be a very important storyline." Just before the script reading for the season 10 finale, Rhimes summoned McCeary to inform her of Maggie's true identity. "I was really psyched" McCeary revealed when Rhimes informed her of Maggie's lineage. "I felt really honored to be the one to accept the challenge." However, it wasn't until McCeary experienced the reactions to Maggie's existence from her fellow cast mates that McCeary realized just how big of a deal the character would be.

For the thirteenth season, Vulture Writer, Maggie Fremont spoke positively about the character: "It’s never easy for a long-running series to introduce a new character, especially when that character is meant to immediately fit in with the rest of the ensemble. But when Maggie Pierce arrived in season ten, that’s exactly what Grey’s Anatomy did. It could’ve been easy to dislike her — she showed up to take over cardio as Cristina Yang was leaving, for chrissakes! She was yet another one of Meredith’s long-lost sisters. The cards were really stacked against Maggie Pierce. Yet, thanks to the Writers and Kelly McCreary’s terrific performance, Maggie was immediately endearing. She is weird and neurotic and cheerful. She is nothing like Cristina, but she fills a void that Meredith needs filled in order to function. Can you really imagine Grey’s without Maggie Pierce?"