Gifty is a 28-year-old Ph.D. candidate in neuroscience who attends Stanford University in California. Gifty and her family (Gify, her mother and father, and Gifty's sibling, Nana, who Gifty often describes as "brilliant") came to the United States from Ghana in search of a better life in Huntsville, Alabama. Despite coming from a vastly different culture, Gifty and her family become fully accustomed to the United States and its culture and customs. But Gifty's parents were met with tremendous racism and were unable to find stable work of any significance.
Gifty's mother, however, is struggling with a deep depression. The kind of depression few people have in their lives, and even fewer escape. One day, while experimenting on Gifty gets a call that her mother is not feeling well and is likely in a deep depression, something which she had previously experienced once before in her life, memories of which overwhelm Gifty. Despite this, Gifty decides to send for her mother; her mother, in turn, quickly travels to Gifty.
When Gifty's mother got pregnant with Gifty, she had deep feelings of sadness. From the beginning, Gifty was unwanted. And Gifty was reminded throughout her entire life that she was unwanted, something that she internalized and caused her profound pain.
As a result of Gifty being unwanted and Nana being treasured, the entire family looked at Nana — who was a gifted athlete — as a kind of God. Eventually, Gifty and Nana's father leave on what he says is a short trip back to Ghana. But he never returns.
Depressed and shaken by his father's abandonment, Nana quits playing soccer (and all sports until high school). After getting injured playing basketball in high school, Nana becomes addicted to opioids and eventually dies when Gifty is eleven. This causes Gifty's mother to sink into her first depressive state, rendering her unable to take care of herself — or Gifty.
After Gifty's mother attempts to take her own life, Gifty is taken back to Ghana, where she lives with her aunt and eventually, her father. Once attracted to religion, Gifty no longer expresses interest in religion. She channels her energy and emotions into studying neurology so that she can better understand humans and their brains.
Still, Gifty is unable to help her mother overcome her second bout with depression. However, she eventually reaches out to a colleague, who is able to help Gifty's mother. The book then skips forward, showing that Gifty's mother has died and Gifty running her own neuroscience lab, once again attending church.
