A 12-year-old boy named Ted Wiggins lives in Thneedville, a walled city where all vegetation and plant life are artificial. Ted has a crush on a girl named Audrey and decides to impress her with a "real tree". His grandmother Norma tells him the legend of the Once-ler, who knows what happened to the trees.

Leaving Thneedville in search of the Once-ler, Ted discovers that the outside world is a barren, contaminated wasteland. He finds the elderly Once-ler who agrees to tell him the story of the trees over multiple visits.

The next time he leaves home, Ted encounters Thneedville's greedy mayor Aloysius O'Hare whose company sells bottled oxygen to the polluted city. Explaining that trees and the oxygen they produce freely pose a threat to his business, O'Hare pressures Ted to stay in town, but Ted continues to visit the Once-ler.

The Once-ler recounts how, as a young inventor, he arrived in a lush forest of animals and Truffula trees. Cutting down a tree, he was confronted by the Lorax, the guardian of the forest who "speaks for the trees". After attempting to force the Once-ler out, the Lorax convinced him not to cut down any more trees. Using the Truffula fibers, the Once-ler created the "Thneed", a knitted article with multiple uses, which became a major success. He harvested the Truffula tufts in a sustainable manner, until his unscrupulous relatives persuaded him to resume chopping down trees to speed up production, leading to enormous profits, but also deforestation and pollution. After harvesting the last Truffula tree, the Once-ler was ruined, abandoned by his family, and became a recluse. The Once-ler was left heartbroken and unbearably guilty for destroying the forest. With the region uninhabitable, the Lorax sent the animals away to find a new place to live, and vanished into the sky. The Lorax left a single word on a small pile of rocks: "Unless".

The Once-ler gives Ted the last Truffula seed in the hopes he can regrow the forest and make others care about trees. Ted returns home to plant the seed which is spotted by O'Hare's city-wide surveillance. Enlisting the help of Audrey and his family, Ted is pursued by O'Hare to the center of town. O'Hare rallies the citizens against Ted, telling them that trees are dangerous and filthy, but Ted uses an earthmover to knock down a section of the city wall revealing the environmental destruction outside. Inspired by Ted's conviction, the crowd turns on O'Hare, whose henchmen strap a jetpack-like helmet to him, causing him to fly away in defeat, and the seed is finally planted.

As time passes, the land begins to recover. New trees sprout, animals return, and the Once-ler reunites with the Lorax.

The film ends with a quote from Dr. Seuss: "Unless someone like you cares a whole awful lot, nothing is going to get better. It's not."

Almost heaven, West Virginia
Blue Ridge Mountains, Shenandoah River
Life is old there, older than the trees
Younger than the mountains, growin' like a breeze
Country roads, take me home
To the place I belong
West Virginia, mountain mama
Take me home, country roads
All my memories gather 'round her
Miner's lady, stranger to blue water
Dark and dusty, painted on the sky
Misty taste of moonshine, teardrop in my eye
Country roads, take me home
To the place I belong
West Virginia, mountain mama
Take me home, country roads
I hear her voice in the mornin' hour, she calls me
The radio reminds me of my home far away
Drivin' down the road, I get a feelin'
That I should've been home yesterday, yesterday
Country roads, take me home
To the place I belong
West Virginia, mountain mama
Take me home, country roads
Country roads, take me home
To the place I belong
West Virginia, mountain mama
Take me home, country roads
Take me home, (down) country roads
Take me home, (down) country roads