Tyus was born in Griffin, Georgia, on August 29, 1945. She was the youngest child of Willie and Marie Tyus. She was also the only girl. With three older brothers to keep up with, Tyus learned early how to hold her own. Her father insisted that Wyomia not be left out by her brothers, no matter what they played. She had an early education in backyard football and basketball and other neighborhood games, playing equally with the boys.
She also had an early education in the inequities caused by racism and sexism. Tyus had to spend an hour on the bus to school each day because the school she could walk to was for white children only. In spite of these difficulties she believed in herself and in working hard to achieve her goals. Tyus explained to Lyn Votava of Ethnic NewsWatch, "Now in my day, this wasn't something women were encouraged to do." Through the love and encouragement of her father and her coach, Tyus was able to focus on her athletic abilities, letting them guide her to a better place.
In high school, she was originally drawn to basketball. In 1960, she was invited to a summer clinic at Tennessee State University (TSU) by the track coach Ed Temple. Tyus discovered her own talent for running through Temple's clinic and became serious about track. That same year, her father died, leaving her without his guidance. Temple would take on an important role in Tyus's life, stepping in where her father once stood.
While still in high school Tyus competed in the Amateur Athletics Union (AAU) Girls' National Championships. She won first place in the 50-yard, 75-yard, and the 100-yard races. She ended up attending TSU in Nashville, Tennessee, based upon Temple's invitation and the fact that it was one of the only universities that offered women athletic scholarships. The women's scholarships were unlike those given to men. While men could focus exclusively on their sports, women were required to work two hours a day for their scholarships.