Uterine fibroids disproportionately affect Black women, and exposure to chemicals from hair relaxers or straighteners ("straighteners") may contribute to fibroid development. We examined the association between straightener use and prevalent young-onset uterine fibroids (diagnosed before age 36 y), as well as incident fibroids (diagnosed age 36-60 y), with a focus on Black women. We also examined differences in associations across birth cohorts as proxies for formulation changes. Data from 4,162 Black women in the Sister Study, a prospective cohort of women 35-74 y of age (enrolled 2003-2009), were analyzed. We used logistic regression to estimate odds ratios (ORs) for the association of straightener use at 10-13 y of age and self-reported young-onset fibroids. We used Cox regression to assess hazard ratios (HRs) for straightener use (age 10-13 y and in 12 months before enrollment) and incident fibroids among 779 premenopausal Black women. Similar analyses were conducted in 40,782 non-Hispanic White women. Over 70% of Black women used straighteners. In comparison with no use, any [ Hair straightener use may be positively associated with fibroid risk. https://doi.org/10.1289/EHP14493.