When Curious George is offered a special space mission, Ted (The Man in the Yellow Hat) can't deny his little friend this exciting journey, especially after Curious George completes the training. But when he crash-lands in Africa, a worried Ted goes searching, expecting the worst, only to have it turn out to be the best.

The film chronicles George's adventures as he befriends Kayla, a baby elephant, at a magic circus show and helps her travel across the country to be reunited with her family.Accompanied by his friend, the Man with the Yellow Hat, George travels by foot, train, and truck to reach Kayla's brother and sister in California, only to be accused of elephant-napping and brought all the way back to New York.

With help from a local fisherman, his niece and an adorable baby seal, George embarks on a quest in search of the long-lost shipwreck of legendary sea captain Trumpet Tooter.