This study investigated the causes of Ethiopian teachers' professional misconduct in secondary schools. The researchers employed a descriptive survey design with quantitative and qualitative approaches and collected the data from 404 teachers, ten principals, and five district education office experts via questionnaires and interviews. The researchers analyzed the quantitative data using percentage, frequency, mean, and standard deviation, while the qualitative data through a reflexive thematic analysis technique with verbal narration. The findings disclosed that multifaceted factors as the causes of professional misconduct of secondary school teachers. Such factors include teachers' financial constraints, lack of appropriate training on professional ethics, teachers' negative attitude towards their profession, a mismatch between policy and context, unfriendly working environment, lack of supervision, changes in the curriculum, the community's unfavorable attitude towards teachers and the teaching profession, student-related factors, poor school leadership, and teachers' low commitment to their duties and responsibilities. We recommend that since the causes are multiple and interlinked with each other, the move towards searching for a solution requires holistic, integrative, and systematic approaches in terms of policy directions and continuous intervention practices at different levels of the education system.