Moore made her feature film debut in 2001, with a minor voice role in Dr. Dolittle 2, before playing a supporting role in the comedy The Princess Diaries. She received recognition for her starring role in the romantic drama A Walk to Remember (2002). Her subsequent film credits include Chasing Liberty (2004), Saved! (2004), Racing Stripes (2005), Because I Said So (2007), License to Wed (2007), Love, Wedding, Marriage (2011), 47 Meters Down (2017), The Darkest Minds (2018), and Midway (2019). Moore also voiced Princess Rapunzel in the Disney animated fantasy musical film Tangled (2010).

From 2016–2022, Moore starred as Rebecca Pearson in the NBC family drama series This Is Us, receiving nominations for a Golden Globe Award and a Primetime Emmy Award. In 2019, Moore was awarded a star on the Hollywood Walk of Fame.

The novel's 1950s setting was changed to the late 1990s to early 2000s for the film, as the producers were concerned it might not appeal to teenage audiences. The film was shot in the summer of 2001 for 39 days in Wilmington, North Carolina, with many of the sets borrowed from the television series Dawson's Creek. The film, as with the book, is dedicated to Sparks' sister Danielle, whose cancer-afflicted life inspired the story.

A Walk to Remember was theatrically released on January 25, 2002, and was a box office success, grossing $47.5 million against its $11.8 million budget. The film received generally negative reviews from critics, most of whom criticized its blandness and predictability, while others praised its sincerity and the lead actors' performances. The film was released on DVD in July 2002, and a "Family-Edited Version" was later released in December.