The aim of this study was to assess the prevalence of malocclusion and its association with socio-demographic characteristics, caries experience, and level of oral hygiene in 12- to 14-year-old schoolchildren residing in two socio-economically different districts of Tanzania. A total of 1601 children (mean age 13 years, 60.5 per cent girls) attending 16 primary schools in Kinondoni and Temeke districts participated in a clinical examination and were interviewed in school settings. Chi-square and multiple logistic regression models were used to test for statistically significant differences between different groups. The results showed that 63.8 per cent (62.6 per cent in Kinondoni and 66.0 per cent in Temeke) of the subjects had at least one type of anomaly, with a midline shift (22.5 per cent), spacing of at least 2 mm (21.9 per cent), and an open bite (16.1 per cent) being the most frequently recorded. The majority (93.6 per cent) of the children showed a Class I molar relationship. Class II and Class III malocclusions were registered in 4.4 and 2.0 per cent, respectively. Multiple logistic regression analyses, controlling for socio-demographic factors, showed that the odds ratio for having an open bite was 1.8 if residing in a less socio-economically privileged district. Subjects with decayed, missing, and filled teeth (DNFT) (>0) were 1.7, 2.1, 2.4, and 1.7, respectively, more likely to be diagnosed with a malocclusion, a midline shift, Angle Class II and III, and an open bite. Schoolchildren with fair/poor oral hygiene were less likely than their counterparts with good oral hygiene to be diagnosed with a midline shift. Malocclusions were prevalent in the Tanzanian children investigated and were associated with environmental factors in terms of caries experience and residing in a less affluent district. Preventive programmes to combat the prevalence of malocclusion are recommended.