The strong connection between information and communication technology (ICT) and educational innovation has been acknowledged by literature, and previous studies have shown the effects of various ICT factors on teacher innovativeness, but international evidence seems to come much later. Based on a three-level research framework, this study uses data from 42 countries participating in the 2018 round of Teaching and Learning International Survey (TALIS) to examine the relationships between ICT-related factors and teacher innovativeness, and how ICT use for teaching mediates the relationships. The results of three-level modeling demonstrate those significant predictors, including ICT element in formal education, ICT element in professional development, ICT self-efficacy, and the ICT use for teaching, all at the teacher level but not the school or country level. The results of three-level mediation modeling support the mediation role of the ICT use for teaching and uncover three indirect paths at the teacher level. Implications for how to enhance teacher innovativeness by facilitating ICT integration are discussed.