This study compares the family financial and employment impacts of having a child with fragile X syndrome (FXS), autism spectrum disorder (ASD), or intellectual disabilities (ID). Data from a 2011 national survey of families of children with FXS were matched with data from the National Survey of Children with Special Health Care Needs 2009–2010 to form four analytic groups: children with FXS (n = 189), children with special health care needs with ASD only (n = 185), ID only (n = 177), or both ASD and ID (n = 178). Comparable percentages of parents of children with FXS (60%) and parents of children with both ASD and ID (52%) reported that their families experienced a financial burden as a result of the condition, both of which were higher than the percentages of parents of children with ASD only (39%) or ID only (29%). Comparable percentages of parents of children with FXS (40%) and parents of children with both ASD and ID (46%) reported quitting employment because of the condition, both of which were higher than the percentages of parents of children with ID only (25%) or ASD only (25%). In multivariate analyses controlling for cooccurring conditions and functional difficulties and stratified by age, adjusted odds ratios for the FXS group aged 12–17 years were significantly elevated for financial burden (2.73, 95% CI 1.29–5.77), quitting employment (2.58, 95% CI 1.18–5.65) and reduced hours of work (4.34, 95% CI 2.08–9.06) relative to children with ASD only. Among children aged 5–11 years, the adjusted odds ratios for the FXS group were elevated but statistically insignificant for financial burden (1.63, 95% CI 0.85–3.14) and reducing hours of work (1.34, 95% CI 0.68–2.63) relative to children with ASD only. Regardless of condition, cooccurring anxiety or seizures, limits in thinking, reasoning, or learning ability, and more irritability were significantly associated with more caregiver financial and employment impacts. Proper management of anxiety or seizures and functional difficulties of children with FXS or other developmental disabilities may be important in alleviating adverse family caregiver impacts.