Objectives: This study aims to determine the prevalence of dental fluorosis and the factors associated with dental fluorosis among 12-15 years old female school children in southern sub-population of Saudi Arabia. Methodology: A community-based, cross-sectional survey of 486 school children (females), 12-15 years age group in southern sub-population of Saudi Arabia using. Clinical examinations were performed using the Dean’s index by WHO 2013. A pre-tested questionnaire was used to gather exploratory data on Demographics, Socioeconomic conditions, Access to dental service and exposure to various sources of fluoride. Bivariate associations were examined using the Chi-square and Chi-square trend tests to evaluate the association of selected risk factors with the presence or absence of dental fluorosis. Samples of water were collected from water sources consumed and analyzed. Results: The overall prevalence of dental fluorosis in our study sample was 59.05% and the Community Fluorosis Index (CFI) was 0.4. Questionable fluorosis (50.21%) was the commonest fluorosis seen. The principal factor associated with the presence of dental fluorosis was the frequency of tooth brushing and the use of fluoride supplements with a p-value of 0.04060 and 0.0497 respectively. No significant association was seen between dental fluorosis and socioeconomic status or parental education, drinking water and the intake of tea/coffee, consumption of any type of fish.