Prejudice and discrimination represent a major barrier to the recovery and community integration of individuals with serious mental illnesses. Yet, little is known about the diverse ways prejudicial practices are enacted at the workplace beyond blatant discrimination. This paper presents findings about the manifestations of prejudice and discrimination at the workplace. Data were gathered from a national sample of individuals with serious mental illnesses who reported perceiving negative attitudes at work as part of their participation in a larger study on sustained employment (n = 234) and from a subsequent study on workplace psychiatric prejudice and discrimination (n = 202). Qualitative analyses of data collected through two different surveys informed the development of a comprehensive taxonomy that identified a range of prejudicial and discriminatory practices that fell within two contextual domains: work performance and collegial interactions. The specific categories within each of these domains represented a continuum of more subtle to more blatant expressions of psychiatric prejudice and discrimination that influenced workers with mental illnesses through different impact pathways. Study findings informed the development of a broader conceptual framework for understanding and combating psychiatric prejudice and discrimination in employment settings and improving the workplace inclusion and employment outcomes of individuals with serious mental illnesses.