It's Western Australia, 1931 and the Chief Protector of Aborigines, AO Neville (KENNETH BRANAGH), has decided to enforce the law that "half-caste" children of mixed heritage - namely white fathers and Aborigine mothers - must be removed from their homelands so that they won't grow up and then further dilute the Aborigine race.
Accordingly, he's sent one of his men, Constable Riggs (JASON CLARKE), to round up three Aboriginal girls, 14-year-old Molly (EVERLYN SAMPI), her 8-year-old sister, Daisy (TIANNA SANSBURY) and their 10-year-old cousin, Gracie (LAURA MONAGHAN) and take them 1,200 miles from their home at the Jigalong Depot to the Moore River Native Settlement.
They're to be trained there to be domestic servants along with other such girls and are forbidden to speak in their native tongue. Should any of them attempt to escape, a tracker, Moodoo (DAVID GULPILIL), will set out, find and return them to the Settlement.
Yet, Molly can't stand the place, its rules and regulations, or the fact that she's away from her mother (NINGALI LAWFORD) and other family members and friends. Thus, she convinces the two other girls to accompany her in escaping and returning home. Without any real plan or supplies, the girls then make their escape.
Along the way, they eventually come across the rabbit-proof fence - designed to keep rabbits out of the farmlands -- that traverses the entire continent. Remembering that it runs through Jigalong, they decide to follow it. Yet, Neville eventually realizes that they're doing just that and so sends Moodoo and Riggs on a mission to intercept the girls and return them to the Settlement for appropriate punishment.
As the girls make their way across the continent with help from various strangers and former inhabitants of the settlement, including Mavis (DEBORAH MAILMAN), they try to avoid those after them and safely make their way home.