Objective: Studies on the etiology, treatment, and psychosocial effects of clefts among children born with the condition abound. Limited studies, however, have focused on the mothers of these children. This study aimed to explore the immediate reaction of mothers to seeing their children born with a cleft for the first time. Mothers’ knowledge of cleft and the support systems available to them were also explored. Design: Employing a qualitative description approach, data were collected through face-to-face individual in-depth interviews using a semistructured interview guide. Participants and Research Context: Using the purposive and snowballing sampling techniques, 12 mothers who sought treatment for their children with cleft at a Tertiary health facility in Ghana were selected. The ethical principles outlined in the Declaration of Helsinki were followed during data collection. The data obtained were analyzed applying the technique of thematic analysis. Results: Mothers’ first time reaction to seeing their child born with a cleft was that of sadness, worry, and disappointment. Knowledge of cleft among the mothers was low with most of them knowing more about the condition only after the delivery of their child with a cleft. Mothers received support from family members, health care practitioners, nongovernmental organizations, and their partners. Conclusion: To reduce the psychosocial and emotional effects resulting from mothers giving birth to a child with a cleft, information on the condition should be made available to mothers and primary caregivers early enough.