Due to the massive integration of Information and Communication Technologies (ICTs) in higher education, teachers need to be highly digital competent and have positive attitudes to manage their classes effectively. In this regard, the European Framework for the Digital Competence of Educators (DigCompEdu) introduces a paradigm known as 21st-century competence that all teachers should acquire. Recently, scholars have explored the dimension of teachers' digital competence in the 21st century relating to a digital context. Thus, this explanatory study wants to take a step forward to add to the literature the role of university teachers' 21st-century digital competence in their attitudes toward ICT integration. To meet the end, a questionnaire was designed and administered to 350 Iranian university teachers who implemented ICTs in their classes. The result of partial least squares analysis (PLS-SEM) reveals the significant relationship between university teachers' information and data literacy, digital content creation, communication and collaboration, and problem-solving skills with three antecedents of behavioral intention and actual behavior for employing ICTs. Related pedagogical implications are addressed, such as running some teacher training programs for teachers to escalate their 21st-century digital competencies and making teachers aware of the role of these factors in managing their classes with ICTs.