Cheryl Brown was born in 1950 to Oliver L. and Leola (Williams) Brown. Following her family's involvement in the landmark Brown v. Topeka, Kansas Board of Education, Brown attended public schools in Topeka, Kansas and Springfield, Missouri. She earned a Bachelor of Arts degree from Baker University (Baldwin, Kansas) and a Master of Science degree in Counseling from Emporia State University. In 1972, Cheryl Brown married Larry Henderson. She worked as a classroom teacher and, from 1979 to 1994, as a consultant to the Kansas State Board of Education. In 1988 she co-founded the Brown Foundation for Educational Equality, Excellence, and Research and served as its Executive Director. In 2010 Henderson became Superintendent of the Brown v. Board National Historic Site.

Henderson served on a number of councils and boards including the Washburn University Endowment Association Women's Alliance Advisory Board, the Kansas Humanities Council board, the Kansas State Historical Society board, and the National Trust for Historic Preservation board. She was also a member of a variety of organizations such as the Topeka Junior League and St. John African Methodist Episcopal Church. For her work Henderson has received a number of honors including being named a Kansan of the Year in 1994.

In 1996 Henderson filed as a Republican candidate for the Kansas 2nd District U.S. House of Representatives seat, running against two fellow Republicans, Jim Ryun and Douglas S. Wright, as well as Democrat John Frieden. Henderson fell in the primary with 10,923 votes (to Ryun's 48,602 and Wright's 19,410). Two years later she campaigned against Annie Kuether for the Kansas House of Representatives, 55th district seat. Although Henderson won the primary (earning 1657 votes to Kuether's 1045), she lost the general election (2244 to 3414).

The Henderson's have a son, Christopher.