When she won the role, she moved to New York City with her mother and her younger siblings to film Wonderstruck.

She used American Sign Language interpreters to communicate on set and also received a tutor to continue schoolwork while filming.

[2] Vanity Fair's Charles Bramesco said of her casting, "A Utah native without any major film credits to her name, young Simmonds is expected to make quite a splash both as a new face in the industry as well as an icon for deaf and otherwise sensory-disabled actors.

"[10] When Wonderstruck premiered at the 2017 Cannes Film Festival, the Associated Press's Jake Coyle said Simmonds's screen debut was "hailed as a breakthrough".

[12] In 2018, Simmonds starred in the horror film A Quiet Place as the deaf daughter of a hearing couple, played by John Krasinski and Emily Blunt.

[16] In 2018, Simmonds appeared in a two-episode arc in the third season of the Disney Channel television series Andi Mack.

[19] In October, Simmonds was cast in a lead role in the pilot for the TV series Close Up on Freeform,[20] and production took place later in the year in Vancouver.

[28] Simmonds said that acting on Broadway demands more exaggerated expressions than in film or TV, due to the need for audience visibility.

[30] In July 2021, Simmonds partnered with Circle of Confusion Television Studios to star in and executive produce a TV adaptation of the 2022 deaf-themed book True Biz by Sara Nović.

[33] Following Simmonds's 2017 debut in Wonderstruck, a Utah-based news outlet reported, "Millie plans to continue both acting and advocating for the deaf community.

[35] In 2020, with the commercial release of A Quiet Place Part II being postponed to the following year due to the COVID-19 pandemic,[36] Simmonds and a speech-language pathology clinical fellow designed a face mask that includes a transparent panel to allow lip-reading and facial expressions to be seen.

Simmonds partnered with fair-trade fashion brand Rafi Nova to make the masks and to have net proceeds go to deaf and hard-of-hearing organizations.

[40] In a 2023 interview, she advised young deaf individuals aspiring to enter the entertainment industry to advocate for themselves and clearly communicate their needs.