The role of motivation in chemistry learning has long been explored and has become an exciting research topic worldwide. The aim of this study was to explore whether gender, class and students' anxiety influenced the motivation to learn chemistry among upper-secondary school students in Indonesia. The Chemistry Motivation Questionnaire II and the Chemistry Anxiety Questionnaire were used to examine the influence of multiple predictors through multiple linear regression analysis tests. Participants in this study were 1,211 upper-secondary school students in Indonesia. This study proves that gender has a significant influence on students' motivation to study chemistry, with female students being more motivated to study chemistry than male students. Interesting research results can be seen in the anxiety variable anxiety, specifically in the chemistry learning anxiety aspect, which has a negative correlation with motivation to study chemistry. The regression model of the three factors revealed in this study accounts for 13.8% of the overall proportion of upper-secondary school students' motivation to study chemistry in Indonesia. The results of this study were corroborated using the interview transcript data with 10 students, who extracted several other predictors to influence motivation to study chemistry, including learning experience, learning environment, and digital literacy.