Background: Consideration of sex‐ and gender‐related factors is critical for understanding and supporting health and wellbeing. Although both sex and gender influence people with developmental disabilities, there is relatively little research on these factors and their influences among individuals with fetal alcohol spectrum disorder (FASD), a complex neurodevelopmental disability impacting an estimated 4%–5% of the population. Understanding sex‐ and gender‐related differences in FASD is needed to facilitate evidence‐informed assessment, treatment planning, and advocacy. To begin unpacking these factors, we investigated sex‐based differences in clinical presentation and experiences among individuals assessed for FASD across the lifespan. Methods: We analyzed 2574 clinical records from 29 FASD diagnostic centers in Canada. Participants ranged in age from 1 to 61 years (mean 15.2 years), and more than half (58.3%) were male at birth. Study variables included participant demographics, physical indicators of prenatal alcohol exposure (PAE), neurodevelopmental impairment, FASD diagnosis, co‐occurring physical and mental health diagnoses, and environmental adversity. Results: There were no significant differences between males and females with respect to FASD diagnostic outcome or physical indicators of PAE. However, males experienced significantly more neurodevelopmental impairment. Females experienced higher rates of endocrine problems, anxiety, and depressive/mood disorders, whereas males had higher rates of attention deficit‐hyperactivity disorder, conduct disorder, and oppositional defiant disorder. Adversity also differed by sex, with females experiencing higher rates of trauma and legal problems with victimization/custody, and males having more difficulties with school and offending/incarceration. Sex‐based differences were most apparent in adolescents (13–17 years) and adults (≥25 years). Conclusions: Individuals with PAE/FASD experience notable sex‐related differences in clinical presentation and experiences across the lifespan. Findings from this study should help to guide researchers, service providers, and policy makers to improve FASD screening, diagnosis, and intervention and better address the needs of individuals with PAE/FASD of all genders. [ABSTRACT FROM AUTHOR]