The Watsons Go to Birmingham was the first of Curtis's novels, and is arguably the one he is most remembered for. It was published by Yearling in 1995 and was written primarily for middle-grade readers, typically ages 10 to 13. This novel tells the story of an African-American family living in Flint, Michigan. The first half of the book serves mainly to clue readers into various events in the narrator's (Kenny's) life and lays out Kenny's relationship with his older brother, while the second half is more plot-driven. This later section revolves around the family's decision to drive to Birmingham, Alabama, to drop off Kenny's delinquent older brother Byron, who is meant to live with his strict grandmother for a summer and hopefully become more agreeable.

The novel takes place in 1963, right in the middle of the Civil Rights Movement; while it is a children's novel, the themes of discrimination, segregation, and prejudice are still prominent. The 16th Street Baptist Church bombing, a real historical event that took place on September 15th, 1963, is a major event in this book.

Curtis has singled out this novel as the writing project that showed him what he wanted to do with the rest of his life. As Curtis's first published book after a series of dull jobs in his hometown of Flint, Michigan, The Watsons Go to Birmingham put his career on an entirely new track. Curtis's work is influenced by bits of reality, such as conversations, characteristics of family and friends, and historical events. He also has also declared that Byron, the elder brother in this novel, is one of his favorites among his own characters, since this young man is struggling to find himself.

The Watsons Go to Birmingham was a runner-up for the Newbery Medal, and has been named a top book of the year many times by a number of different publications. The novel was named one of the New York Public Library's Great Children's Books of the Last 100 Years.

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