Research on grit indicates that perseverance positively predicts academic achievement. Yet, the mechanisms through which perseverance might lead to academic success remain less explored, particularly in cross-cultural research. The current study investigated such mechanisms by examining possible mediating effects of students’ use of self-regulated learning strategies (control, memorisation, and elaboration) on the predictive relation of students’ perseverance on their academic achievement, in students from East Asian and Anglo-Saxon English speaking Western countries. The sample came from the OECD PISA study and included 24,352 population-representative 15-year-old students from Hong Kong, the Republic of Korea, Australia, New Zealand, Scotland, and the US. Results revealed that perseverance had a more positive association with achievement in East Asian cultures than Western cultures. Control strategy was stronger positive mediators of achievement in Western countries, whereas memorisation and elaboration strategy use and instrumental motivation more negatively mediated the effect of perseverance on achievement in Western countries.