Background: There is a growing global acknowledgement that improving child survival rates is no longer sufficient. Emphasis is shifting to the improvement of health and developmental trajectories in early childhood. Screening and measurement of these trajectories in low and middle income countries is difficult, however, as they currently rely on developmental tests standardised among populations of children growing up in resource rich environments. Methods: This paper presents a comparison of one such tool adapted for use with children living in Southern Africa to children from the United States, Norway, Korea and Spain. The Ages and Stages Questionnaire version 3 (ASQ-3) was adapted and administered to 853 children living in South Africa and Zambia. Results: Children in southern Africa were found to perform significantly better than children from other countries early in life, especially in the domains of communication, gross motor and fine motor skills. By the age of five, children in southern Africa were performing significantly worse than their peers in the domains of fine motor and problem-solving. Conclusion: The results indicate the applicability of the ASQ-3 in southern Africa and point to the importance of early interventions to protect the early good development of African children in order to promote positive life trajectories.