A large body of literature suggests that attitudes toward technology and its educational use are important determinants of technology acceptance and integration in classrooms. At the same time, teachers' Technological, Pedagogical, and Content Knowledge (TPACK) facilitates the meaningful use of technology for educational purposes. Overall, attitudes toward technology and TPACK play a critical role for technology integration and have been in the focus of many empirical studies. Albeit the attention that has been paid to these two concepts, their relation has not been fully understood. The present study contributes to the advancement of this understanding by examining the relations between three core technology attitudes (i.e., general attitudes towards ICT, attitudes towards ICT in education, and ease of use) and TPACK self-efficacy beliefs, based on a sample of N = 688 Flemish pre-service teachers in 18 teacher-training institutions. Using a variety of structural equation modeling approaches, we describe the TPACK-attitudes relations from multiple perspectives and present a substantive-methodological synergism. The analyses revealed that the attitudes toward technology and TPACK self-beliefs were positively related; yet, differences across the attitudes and TPACK dimensions existed, pointing to the delineation of general and educational perspectives on the use of ICT.