Instructional quality is associated with better academic outcomes for students. This study aimed to investigate how teachers' job satisfaction was associated with clarity of instruction and cognitive activation as measures of instructional quality. In addition, we investigated whether this association between teachers' job satisfaction and instructional quality was mediated by teacher-student relationships. Drawing on the 2018 Teaching and Learning International Survey (TALIS), we compared participants from both Eastern (N = 27,106; Japan, Taipei, Korea, Shanghai) and Western sociocultural contexts (N = 20,209; Canada, Australia, New Zealand, United States, United Kingdom). Multilevel structural equation modelling results indicated that teachers' job satisfaction was positively associated with instructional quality across Eastern and Western settings. The relationship between teachers' job satisfaction and instructional quality was partially mediated by better student-teacher relationships. There were some differences between the cultural settings in how job satisfaction correlated with clarity of instruction and cognitive activation. We suggest that these differences may be accounted for by cultural characteristics leading to different approaches to teaching. Our results suggest that teachers' job satisfaction and the quality of classroom-level relationships may be important indicators of positive instructional outcomes. While schools focus on student outcomes, they should also address teachers' job satisfaction and prioritise the importance of relationships between teachers and students in classrooms.