At the start of The Watsons Go to Birmingham—1963, all five members of the Watson family are huddled in blankets to fend off the cold in their apartment. Mrs. Watson is certain they will freeze to death. Through the perspective of ten-year-old Kenny, readers are introduced to the quirky behaviors of his family. Kenny is convinced that everyone in their neighborhood and school thinks of them as "The Weird Watsons."

Through Kenny’s viewpoint, we explore his complicated love/hate relationship with his older brother, Byron, often called By. Kenny’s feelings about By fluctuate between fear of By’s bullying, admiration for By’s "fantastic adventures," and enjoyment of By’s occasional acts of kindness.

Kenny often tries to reconcile how a bully like By can have such a great sense of humor. By’s antics include a narcissistic moment where his lips get stuck to the car’s side-view mirror—known to the kids as the "Brown Bomber"—after he kisses his reflection one cold winter morning. This happens as the family prepares to visit an aunt to escape their freezing apartment. In another instance, By straightens his hair against his parents' wishes, leading Dad to cut it all off and shave his head. These and other humorous events draw readers into the close-knit life of this Black American family living in Flint, Michigan, in 1963. Kenny often finds himself on the sidelines, sometimes admiring By’s rebellious streak and other times fearing the consequences of By’s poor decisions.

Dad and Momma, as the Watson children call their parents, are dedicated to raising respectful, well-behaved children who make good choices and uphold high moral standards. Realizing they haven’t fully succeeded with their eldest, Dad and Momma decide to take By to Birmingham to stay with Grandma Sands, a strong-willed woman who will set him straight. Although they are aware of some violence in the South due to the Civil Rights Movement, Grandma Sands assures them that her area is peaceful.

Upon arriving in Birmingham, Grandma Sands welcomes them with open arms and a home filled with love for her daughter and family. By’s only memory of Grandma Sands is from when he was four years old, and he has convinced Kenny and their kindergarten-aged sister, Joetta, that she is a mean old woman. Kenny and Joetta have never met her before their visit in the summer of 1963, and By’s description has frightened Kenny. Both Kenny and By evaluate her and conclude that By could easily handle this so-called mean old woman.

Kenny and his family arrive in Birmingham just as the violence reaches Grandma Sands’s neighborhood. Initially, Kenny almost drowns, but Byron rescues him. Then, a nearby Baptist Church is bombed on a Sunday morning. For the rest of the story, Kenny struggles with his emotions, which are intertwined with the “Wool Pooh” he encounters first during his near-drowning incident and then again at the bombed church.