Objective: The present study aimed to identify distinct trajectories of parental illness uncertainty appraisals among parents of children born with atypical genital appearance due to a Difference of Sex Development (DSD) over the first year following diagnosis. It was hypothesized that four trajectories would emerge, low stable, high stable, decreasing, and increasing profiles, and that key demographic, familial, and medical factors would predict these trajectories. Methods: Participants included 56 mothers and 43 fathers of 57 children born with moderate to severe genital atypia. Participants were recruited from eleven specialty clinics across the United States. Growth mixture modeling (GMM) approaches, controlling for parent dyad clustering, were conducted to examine profiles of illness uncertainty ratings over time. Results: A three-class GMM was identified as the best fitting model with freely estimated intercept variances. The three profiles were labeled as “Moderate Stable” (63.8%), “Low Stable” (20.9%), and “Recovering” (15.3%). Those in the Recovering class were less likely to have a Congenital Adrenal Hyperplasia diagnosis (versus other conditions) and may also be more likely to report higher anxious symptoms at baseline. Conclusions: Findings highlight the nature of parents’ perceptions of ambiguity and uncertainty about their child’s diagnosis and treatment shortly following their child’s birth. Future research is needed to better understand how these trajectories might shift over the course of the child’s development. Tailored, evidence-based interventions are needed to support families coping with uncertainty while raising a child with chronic health needs and bolster long-term family functioning.