In the opening pages of The Watsons Go to Birmingham - 1963, all five members of the Watson family are sitting wrapped in blankets against the cold of the apartment. Mrs. Watson is convinced they are going to freeze to death.

Through the eyes of ten-year-old Kenny, the reader learns about the crazy antics of his family. Kenny believes that everyone in his neighborhood and school must think his family is strange—"The Weird Watsons".

Through Kenny's eyes we view his tenuous love/hate relationship with his older brother Byron, often called By. Kenny's feelings about By swing between fear of By's bullying tactics, awe of By's "fantastic adventures," and pleasure in By's sometimes unexpected kindness.

Kenny frequently tries to understand how a bully can have such a great sense of humor. By's craziness includes a narcissistic attitude which freezes his lips to the side-view mirror of the family's car, known to the children as the "Brown Bomber," as he kisses himself one freezing winter morning when the family decides to go to an aunt's house to escape the cold in their apartment. When he has his hair straightened against the express wishes of his parents, Dad cuts it all off and shaves By's head. These and other hilarious incidents draw the reader into the intimacy of this African-American family living in Flint, Michigan, in 1963. Kenny stands on the sidelines sometimes admiring By's rebellion and slow slide towards trouble and other times fearing the consequences of By's not-too-bright choices.

Dad and Momma, as the Watson children call their parents, are determined to raise respectful, well-behaved children who make good choices and possess high moral standards. Realizing they have been unable to instill fully their standards in their oldest child, Dad and Momma decide to take By to Birmingham and leave him with his Grandma Sands, a strong woman who will bring him to his senses. They know there is some violence in the South with the beginnings of the Civil Rights Movement, but have been assured by Grandma Sands that it is quiet around her.

In Birmingham, Grandma Sands meets them with arms open wide and a home filled with love for her daughter and family. By's only recollection of Grandma Sands is when he was four years old, and he has convinced Kenny and their kindergarten sister, Joetta, that she is a mean old woman.

Kenny and Joetta have never met her prior to their visit in the summer of 1963, and By's description of Grandma Sands has scared Kenny. Kenny and By both take her measure and decide By can easily take this mean old woman down.

Kenny and his family have gone to Birmingham just as the violence moves into Grandma Sands neighborhood. First, Kenny nearly drowns and By saves him, then the nearby Baptist Church is bombed on Sunday morning. In the remainder of the story, Kenny must deal with his emotions that are tangled up with the "Wool Pooh" he meets first in his near drowning experience and then a second time in the bombed church.