In the context of information and communication technology (ICT)-enhanced teaching, teacher well-being plays a crucial role in promoting teaching effectiveness and students' learning achievement. Drawing on the interactionist model of teacher well-being, this study investigated university teachers' well-being (e.g., emotional exhaustion and teacher engagement) in ICT-enhanced teaching and its associations with their self-efficacy (e.g., classroom management, instructional strategy and course design) and teaching support (e.g., autonomy support, teaching resources and peer support). The results of an online questionnaire survey conducted among 836 university teachers in China indicated that the enhanced integration of ICT into teaching practices neither impaired teacher engagement nor caused them significant emotional exhaustion. Instead, adequate teaching resources and autonomy support contributed positively to both teacher self-efficacy and engagement. Increased efficacy in course design and classroom management alleviated their emotional exhaustion. Moreover, teacher self-efficacy significantly mediated the effects of autonomy support on emotional exhaustion and teacher engagement. These results have practical implications for understanding and promoting university teachers' well-being as well as teaching effectiveness in ICT-enhanced teaching environments.