The present study examined the predictors of information technology (IT) integration in secondary school mathematics lessons. The predictors pertained to IT resource availability in schools, school contextual/institutional variables, accountability pressure faced by schools, subject culture in mathematics, and mathematics teachers’ pedagogical beliefs and practices. Data from 32,256 secondary school students from 2,519 schools in 16 developed economies who participated in the Program for International Student Assessment (PISA) 2012 were analyzed using hierarchical linear modeling (HLM). Results showed that after controlling for student-level (gender, prior academic achievement and socioeconomic status) and school-level (class size, number of mathematics teachers) variables, students in schools with more computers per student, with more IT resources, with higher levels of IT curricular expectations, with an explicit policy on the use of IT in mathematics, whose teachers believed in student-centered teaching-learning, and whose teachers provided more problem-solving activities in class reported higher levels of IT integration. On the other hand, students who studied in schools with more positive teacher-related school learning climate, and with more academically demanding parents reported lower levels of IT integration. Student-related school learning climate, principal leadership behaviors, schools’ public posting of achievement data, tracking of school’s achievement data by administrative authorities, and pedagogical and curricular differentiation in mathematics lessons were not related to levels of IT integration. Put together, the predictors explained a total of 15.90% of the school-level variance in levels of IT integration. In particular, school IT resource availability, and mathematics teachers’ pedagogical beliefs and practices stood out as the most important determinants of IT integration in mathematics lessons.