Dental caries is a chronic infectious disease that causes demineralization of dental hard tissues. Dental caries was declared a pandemic by World Health Organization (WHO) in 2005 because of its high global prevalence and severe consequences. The prevalence of dental caries varies worldwide between 60% and 90%. In Kenya approximately 50% of children aged between 13-15 years have dental caries. The main objective of the study was to determine the association between dental caries and oral health knowledge and practice among children in Nairobi West and Mathira West Districts. A cross-sectional study was conducted among 639 children aged 12 years attending public primary schools in Nairobi West and Mathira West districts. A semi-structured questionnaire was used to determine the level of knowledge and practices employed. Oral screening was performed using WHO recommended methods. Dental caries was measured using the Decayed, Missing, Filled Teeth (DMFT) index. Nairobi West District had significantly higher caries prevalence of 37.5% than Mathira West District which had a prevalence of 24% (p<0.05). The mean DMFT in Nairobi West District was 0.76 ± 1.2 while in Mathira West District it was 0.36 ± 0.7. On multivariate analysis knowing that a toothbrush should be changed after three months (OR 3.2) and high consumption of soda (OR 3.0) were found to be significant risk factors for dental caries in Nairobi West District. In Mathira West District having a caregiver with no formal education (OR 4.3) was a significant risk factor for dental caries. The study shows the need for intensive oral health promotion in urban areas to reduce the higher prevalence of dental caries. The school health policy should be used to promote oral health by provision of oral health instructions and educating on harmful dietary practices particularly soft drinks. Caregivers should be encouraged to take their children for regular dental check-ups.