Although hypoactive sexual desire dysfunction (HSDD; low sexual desire with personal distress) negatively impacts well-being, contemporary life-course prevalence data for HSDD are lacking. To document, in an epidemiologic study, the prevalence of low sexual desire with associated distress (epidemiological HSDD [eHSDD]), and associated psychosocial factors in Australian women. A cross-sectional study of 10,554 women, aged 18-79 years, recruited from the community was performed. Low desire was determined by corresponding questions in the Profile of Female Sexual Function and Female Sexual Function Index. HSDD was defined as having a low desire and Female Sexual Distress Scale-Revised score of ≥11. Clinicians need to be aware that young women often experience sexually related distress whereas low desire with associated distress is most common in women at midlife. The majority of the participants were partnered (66.5%) and 38.9% were recently sexually inactive. Low desire prevalence increased from age 18-24 years to 75-79 years (27.4%, 95% CI 25.5-29.3 vs 91.6%, 95% CI 88.3-94.1, P < .001). Just over half of all participants aged 25-39 years had sexually related personal distress, after which the prevalence declined with age (P < .001). 10,259 participants provided sufficient information for eHSDD classification. eHSDD increased from age 18-24 years (12.2%, 95% CI 10.8-13.7) to 40-44 years (33.4%, 95% CI 28.5-38.8), remained constant until 60-64 years (33.1%, 95% CI 28.3-38.4), and progressively declined to 7.3% (95% CI 4.8-10.9) by 75-79 years. HSDD was significantly, positively associated with being partnered (P < .001), sexually inactive (P < .001), more educated (P = .001), and psychotropic medication use (P < .001), and negatively with Asian ethnicity (P < .001). This study involved the assessment of desire using a single question derived from the Profile of Female Sexual Function or the Female Sexual Function Index. eHSDD is most prevalent at midlife. Furthermore, the likelihood of eHSDD is greater for women who are partnered, sexually inactive, more educated, or taking psychotropic medications. Taken together these findings should aid health professionals in identifying women most at risk of eHSDD. Zheng J, Islam RM, Bell RJ, et al. Prevalence of Low Sexual Desire With Associated Distress Across the Adult Life Span: An Australian Cross-Sectional Study. J Sex Med 2020;17:1885-1895.