Growing up in Denver, Colorado, she enjoyed creating objects from spare materials around her house and making small sketches for her high school classmates. She took art classes as an undergraduate at Agnes Scott College but only declared as studio art as her major in her junior year, when she studied abroad in Italy and enrolled in a painting class. After college, she taught special education and painted her students in her spare time before deciding to fully focus on her studio practice. When she arrived at the MFA program at the Yale School of Art, she found that her lack of training in traditional artistic methods allowed her to uninhibited in her experiments with figuration.

In 2013, Casteel developed an approach centered around portraits of Black subjects—many of whom are her friends, family, or acquaintances. Her subjects look directly at the viewer and assert their identity, vulnerability, and dignity. Her canvases feature people from the communities in which she lives, such as street vendors and business owners in Harlem or former classmates from her time at Yale, all of whom she photographs and studies to construct her compositions. Her subjects’ skin is not always black, but an array of red, green, yellow, and blue, alluding to the slipperiness of categorizing identity solely based on skin color. On the responsibility and importance of her work, Casteel notes: “I think that that is bigger than anything else I’ve done in my life—putting people, who have maybe spent their lives feeling invisible in certain ways, front and center and honored in the way that they ultimately deserve to be honored.”

Casteel earned her BA from Agnes Scott College and MFA from the Yale School of Art. From 2016 to 2021, she taught at Rutgers University at Newark. She is the recipient of a MacArthur Foundation Fellowship (2021). The Studio Museum presented her work in exhibitions including Regarding the Figure (2017) and Black Refractions: Highlights from The Studio Museum in Harlem (2019–20).