Simmonds, who read the deaf-themed Juvenile novel Wonderstruck when it was published in 2011, received news of open casting for the film adaptation (released in 2017) from her former drama Teacher and auditioned for a role in the film. She competed with over 250 others. 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. 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." 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". Simmonds was subsequently nominated for several awards for best youth performance (see accolades). The Associated Press also recognized Simmonds as one of eight actors who were Breakthrough Entertainers of 2017.
Simmonds is a native of the U.S. state of Utah. She lives in Bountiful, Utah. She has four siblings; two older and two younger than she. At twelve months old, Simmonds lost her hearing due to an accidental medication overdose. Her mother learned American Sign Language and taught the family so they could communicate with her. When Simmonds was three years old, she started attending the Jean Massieu School of the Deaf, where she participated in its drama club. After completing sixth grade, she mainstreamed at the Mueller Park Junior High School in the fall of 2015. She has performed at the Utah Shakespeare Festival in Cedar City, Utah, and her sole film experience before Wonderstruck was a deaf student's short, "Color the World". Simmonds has a cochlear implant to help her hear.
KSL.com's Liesl Nielsen reported in May 2017, "Millie plans to continue both acting and advocating for the deaf community." In 2018, she starred in the well-received horror film A Quiet Place as the deaf daughter of a hearing couple, played by John Krasinski and Emily Blunt.
