This study is about challenges faced by teachers in implementing the competence-based curriculum in the chemistry subject in public secondary schools in Nyamagana District. The objectives of this study were to determine the influence of teachers' competence, instructional materials, mode of assessment, and lesson plan on the effective implementation of the chemistry curriculum. The study used a mixed research approach and convergent parallel design. It drew a sample of 133 respondents using both probability and non-probability sampling processes for a population of 38,848 individuals. Data was collected using both primary and secondary sources, specifically a questionnaire and an interview. The reliability was tested and the coefficient r = 0.8 was obtained, which hence allowed the researcher to use the tools. Quantitative data collected was analyzed by the use of descriptive statistics with the help of the Statistical Package of Social Science version 21 and presented in tables through frequency and percentage, while qualitative data was coded and analyzed thematically through narratives. The findings of the study revealed that many public secondary schools in Nyamagana do not have enough instructional materials such as laboratory chemicals and apparatus for practical tests, besides inadequate lesson preparations, which are very important factors in enhancing the implementation of the curriculum in chemistry subject. The study concluded that most chemistry teachers in the Nyamagana district had difficulties in lesson planning and implementing competence-based chemistry curriculum. Also, many schools had inadequate instructional materials such as laboratory chemicals, laboratory apparatuses, tables, stools, water, laboratory rules charts, and coats and gloves. The study recommends that the government, with its stakeholders, provide adequate funds for the supply of instructional materials, for effective implementation of the competency-based chemistry curriculum.