AstroBoy - which debuted on Japanese TV in the '60s - is about a super-powered robot boy built by a scientist to replace the son he lost.
Director David Bowers said the 16-year-old would bring a "vitality" to the role.
"It's terrific that Freddie has agreed to play Astro," said Bowers. "He's a remarkably skilled young actor, whose freshness and vitality make him perfect for the role. AstroBoy is a beloved superhero and has captured hearts around the globe for more than 50 years. I can't wait to see where Freddie takes him."
Highmore's credits include The Golden Compass, Finding Neverland, A Good Year and the upcoming The Spiderwick Chronicles.
The film will get a worldwide release next year.