It's London in the 19th century and Alice Kingsleigh (MIA WASIKOWSKA) is a nineteen-year-old who's been jockeyed into a pending arranged marriage with young but square nobleman, Hamish Ascot (LEO BILL). An imaginative and independent young woman, Alice is hesitant to follow in her older sister's footsteps, especially since Hamish doesn't appreciate her view of the world or creative mindset.
Thus, when she spots the White Rabbit (voice of MICHAEL SHEEN), a hare in a waistcoat and carrying a pocket watch, she uses that as an excuse to rush off, not realizing she'll end up falling down a long rabbit hole and into Underland, a recurring place in the one and only dream she's ever experienced since she was a little girl.
There, she finds substances that make her both larger and smaller as well as a fantastical array of characters, many of them speaking animals. Among them is the White Rabbit, twins Tweedledee (MATT LUCAS) and Tweedledum (MATT LUCAS), feisty Dormouse Mallymkun (voice of BARBARA WINDSOR), the bodiless and often vanishing Cheshire Cat (voice of STEPHEN FRY), and a hookah smoking caterpillar by the name of Absolem (voice of ALAN RICKMAN). They're all in debate about whether she's the real Alice or not, and imply that she's been there before, although she believes that and this experience are nothing more than dreams.
Yet, she discovers that her future fate is to defeat a fierce dragon known as Jabberwocky (voice of CHRISTOPHER LEE) that's under the control of the Red Queen (HELENA BONHAM CARTER). By doing so, she'll thus enable that monarch's younger sister, the White Queen (ANNE HATHAWAY), to return to power and thus makes things right in Underland. Unfortunately, the Red Queen knows of Alice's return, and thus has ordered her eye-patched lieutenant, Stayne, the Knave of Hearts (CRISPIN GLOVER) to find the interloper, and he uses bloodhound Bayard (voice of TIMOTHY SPALL) to try to pick up her scent.
Alice finds an unlikely and unusual ally in the form of the Mad Hatter (JOHNNY DEPP) who once made hats for the White Queen, but is now quite crazed apparently from the mercury used in such previous production. He spends much of his time in a perpetual tea party with Dormouse, the equally mad March Hare (voice of PAUL WHITEHOUSE) and occasionally Cheshire Cat, but wants nothing more than the removal of the Red Queen. Considering that's a potentially dangerous stance since the Queen's command for anyone who crosses her path is "Off with their head!" he, Alice and their accomplices must then proceed with all due caution.