There are numerous risks associated with high-rise buildings, which not only affect stakeholders during the design and construction phase but also impact the occupants and the surrounding environment during the post-occupancy phase. While previous studies examined the risks of high-rise building construction, less attention has been paid to the diverse impacts of high-rise buildings on their occupants. To fill this gap, this study applied a mixed-method approach (both quantitative and qualitative) to identify and prioritize their most significant social impacts. First, the possible social impacts of these buildings were identified via a literature review. The interrelationships among the identified factors were then determined by drawing on the opinions of relevant experts. Next, through the quantitative phase, the high-rise residential buildings of District 22 of Tehran were considered as a case study, and according to the opinions of 230 chosen residents, the level of influence of factors on one another was determined. The DEMATEL approach was employed subsequently to analyze the data and identify the most important and influential factors. Finally, through the qualitative phase, in-depth interviews were conducted with residents to explain and validate the results. The most significant and influential impacts identified by this study were anti-social behavior, lack of social cohesion, and lack of social contact with neighbors. This study assists designers and policymakers to adopt strategies that could mitigate the identified impacts and improve occupants’ social wellbeing more efficiently.