Known to be discrediting and discriminatory in nature, scholars have argued that the impact of stigma against persons with lived experiences of mental illnesses (PWLEs) is far worse than living with the symptoms of the conditions itself. Particularly in Asia where mental illnesses tend to be highly moralized, where PWLEs are often conceived as displaying poor character due to Confucius ideology or religious reasons, evidence has shown that stigma against PWLEs is much stronger in Asia than in the Western contexts. Currently, there is limited insights on the origins of mental illness stigma and how stigma is constructed into moralized forms and perpetuated across society. Underpinned by social constructionism, this systematic review and meta-ethnography paper undertook a theory-driven approach to address ‘how is mental illness stigma socially constructed amongst Asians?’ Systematic search for primary qualitative research journal papers was conducted across six databases (PubMed; Embase; PsycINFO; CINAHL; Social Science Database; SCOPUS), yielding 4516 articles. 30 articles were identified for synthesis. Results revealed how historical context of governmental (colonialism; Confucius ideology; industrialization) and religious institutions and country-specific power elites and individuals shaped the constructions of cultural stigma. Cultural stigma permeates societies through culturally dependent language via word-of-mouth (facilitated by collectivism) and media into forms of public stigma, causing a lack of trust between public and PWLEs. Individuals in societies further perpetuate stigma by means of interpreting, labelling anomalies and discriminating PWLEs based on preconceived learnt cultural prejudices that are activated during social interactions, further reinforcing public stigma. Finally, while most PWLEs anticipate stigma and self-stigmatize due to internalization of cultural and public stigma, unique to this study, a small group of PWLEs was able to resist and contest stigma due to holding socially valued roles that ‘matter most’. Recommendations for destigmatization strategies are suggested in view of these findings.