Technological Pedagogical and Content Knowledge (TPACK) is a well-known framework in the field of educational technology. However, there is a dearth of studies that examine the impact of teachers' TPACK on the acceptance of Online Teacher Professional Development (OTPD). This study aimed to examine if TPACK affected secondary school mathematics teachers' acceptance of OTPD. A quantitative method with a cross-sectional survey was employed. Two hundred and ten Indonesian secondary school mathematics teachers completed a 40-item questionnaire based on TPACK and Technology Acceptance Model (TAM). Data were analyzed by structural equation modeling. The findings showed that TPACK constructs were strongly interconnected and significantly affected teachers' acceptance of OTPD. Therefore, this study suggests that TPACK is a valid model to explain teachers' engagement in OTPD.