Background The prevalence of general and disease-specific sexual and reproductive health (SRH) concerns is unknown in the United States (U.S.) female CF population. This study aimed to describe and compare the SRH experiences and behaviors of young women with CF with the general U.S. population. Methods Young women with CF ages 15–24 years from five geographically diverse U.S. CF centers participated in a survey investigating SRH. Results were summarized and compared to the U.S. National Survey of Family Growth (NSFG) using logistic regression adjusting for confounders. Findings A total of 188 young women with CF (mean age 19.7 ± 2.7 years) completed the survey; data were compared to 1997 NSFG respondents (mean age 19.6 ± 0.10 years). Fifty-four percent of women with CF reported having had vaginal sex with a male partner compared to 66% of U.S. women (p = 0.55). Women with CF were less likely to have ever used contraception (55% vs. 74%, p = 0.0001) or have been tested for sexually transmitted infections in the past year (19% vs. 34%, p = 0.001) compared to the general population. Two percent of women with CF reported having ever been pregnant compared to 24% of U.S. women (p < 0.0001). One-third of young women with CF reported perceived pubertal delay, 16% urinary incontinence, 16% sexual dysfunction, and 49% yeast infections. Interpretation Young women with CF face significant SRH concerns and appear to be experiencing gaps in SRH care provision. Opportunities exist for intervention development around this aspect of comprehensive CF care. Funding CF Foundation (KAZMER15A0); U.S. National Institutes of Health (UL1TR000005).