This path analysis of mothers of children with autism aimed to investigate the relationship between maternal burnout and the mother’s subjective reporting of difficulty in childcare, family function, and personality traits. A total of 410 mothers of children with autism (mean age 39.03, SD 7.42) completed four questionnaires: Parental Burnout Measure (PBM-12), International Personality Item Pool—Big Five Markers (IPIP-BFM-20), Flexibility and Cohesion Evaluation Scales (FACES-IV), and a survey on childcare difficulties. Path analysis using two predetermined models was used to examine the interrelations. Both models fit the empirical data equally with a Root Mean Square Error of Approximation (RMSEA) index of 0.000 and a 90% confidence interval (model 1: 0.000–0.052; model 2: 0.000–0.059). Path analysis revealed similar fit indexes for both models: (a) burnout is a mediator between exogenous variables and family functioning, and (b) family functioning is an indirect mediator between exogenous variables and burnout. These findings suggest that increased maternal emotional instability (neuroticism) and conscientiousness can lead to increased family communication problems, which may further lead to a breakdown of the equilibrium in the family system, resulting in the mother’s dissatisfaction with family life and a consequent increased risk of maternal burnout.