In this study, we examined health education practice in Child-to-Child (CtC) classrooms in urban and rural primary school settings in Pakistan to describe and compare practice critically. Structured observations of health lessons were carried out in 67 randomly chosen primary classrooms from Health Action Schools in urban (n = 32) and rural (n = 35) contexts. Health education practices were found to be more “participatory” in rural classrooms than in urban ones. Using a multivariate analysis, we identified three factors that contributed independently to the use of participatory approaches in classroom practices: the HEALTH aggregate (i.e., intensity of health education training, use of a health manual, and regularity of health teaching), teachers’ attendance at staff development workshops, and children’s gender. This study provides insight into a largely unexamined area of health education CtC classroom practice. This research in primary classrooms of Pakistan furthers the understanding of health education classroom practices in the context of professional development of teachers for health promotion.