Research evidence suggests that faculty members' well-being is a serious concern in academia. However, little is known about the academic job demands and resources, which are specific to the professional context and faculty work, that influence faculty well-being. Moreover, the psychological processes how job characteristics lead to well-being outcomes among faculty are to date underexamined. We addressed these gaps and investigated the mediating impact of frustration of basic psychological needs on the relationship between academic job factors and faculty well-being. Survey data were collected from 592 faculties employed in 13 Canadian research-intensive universities. The questionnaire measured faculty perceptions of (a) pressure and support in relation to academic tasks, (b) work-home conflict, (c) workplace frustration of psychological needs, and (d) varied well-being outcomes (engagement, commitment, burnout, and health). Structural equation modeling showed that work-home conflict and low academic resources positively predicted burnout and health problems but negatively predicted engagement. Work-home conflict, academic pressure, and insufficient support predicted greater basic need frustration that in turn negatively influenced faculty well-being. Findings highlight the need for future research to better identify aspects of academic work that obstruct or sustain faculty basic needs in order to provide need supportive academic culture that bolsters faculty well-being.