This study explores the stability and change in maternal life satisfaction and psychological distress following the birth of a child with a congenital anomaly using 5 assessments from the Norwegian Mother and Child Cohort Study collected from Pregnancy Week 17 to 36 months postpartum. Participating mothers were divided into those having infants with (a) Down syndrome (DS; n = 114), (b) cleft lip/palate (CLP; n = 179), and (c) no disability (ND; n = 99,122). Responses on the Satisfaction With Life Scale and a short version of the Hopkins Symptom Checklist were analyzed using structural equation modeling, including latent growth curves. Satisfaction and distress levels were highly diverse in the sample, but fairly stable over time (retest correlations: .47–.68). However, the birth of a child with DS was associated with a rapid decrease in maternal life satisfaction and a corresponding increase in psychological distress observed between pregnancy and 6 months postpartum. The unique effects from DS on changes in satisfaction (Cohen’s d = −.66) and distress (Cohen’s d = .60) remained stable. Higher distress and lower life satisfaction at later assessments appeared to reflect a persistent burden that was already experienced 6 months after birth. CLP had a temporary impact (Cohen’s d = .29) on maternal distress at 6 months. However, the overall trajectories did not differ between CLP and ND mothers. In sum, the birth of a child with DS influences maternal psychological distress and life satisfaction throughout the toddler period, whereas a curable condition like CLP has only a minor temporary effect on maternal psychological distress.