This study investigates the mediating roles of mathematics interest and perseverance on the effects of cognitive activation on mathematics achievement. We analysed data from a large-scale survey involving 25,969 eighth grade students from 86 schools in central China. The results show that (1) cognitive activation had a direct and positive effect on students' mathematics achievement; (2) the positive relationship between cognitive activation and mathematics achievement was prominently mediated by mathematics interest; (3) perseverance partially mediated the relationship between cognitive activation and mathematics achievement; and (4) mathematics interest and then perseverance serially mediated the relationship between cognitive activation and mathematics achievement. The implications of the findings for mathematics teachers are discussed and suggestions are made for future research.