This comparative study investigated the associations between instructional practices and students’ reading performance among 10 top performing regions that participated in the Program for International Student Assessment (PISA) 2018. A nationally representative sample consisting of 80,016 15-year-old students from 5 Asian regions (B-S-J-Z [China], Singapore, Macao, Hong Kong, and Korea) and 5 Western regions (Estonia, Canada, Finland, Ireland, and Poland) were included. A secondary analysis of PISA survey and assessment data was conducted. T test and ANOVA analyses revealed systematic differences in instructional practices of the 10 regions. B-S-J-Z (China) had significantly higher levels of teacher support, teacher-directed instruction, and teacher stimulation than the other sample regions. Asian regions tended to have higher levels of teacher support, teacher-directed instruction, teacher feedback, adaptive instruction, and teacher enthusiasm compared with Western regions, although variations were also found within Asian regions or within Western regions. Hierarchical linear regression (HLR) analyses indicated that reading performance was positively predicted by teacher support, adaptive instruction, teacher stimulation, and teacher enthusiasm, but negatively predicted by teacher-directed instruction and teacher feedback. This study sheds light on the effective instructional practices for optimizing students’ reading performance across different cultural contexts.