Studies and findings regarding the impact of schizophrenia on quality of life (QOL) has been highly variable. This meta-analysis compared QOL between schizophrenia subjects and healthy controls with a focus on standardized measures. A systematic literature search was conducted through Pubmed, PsycINFO, EMBASE, Cochrane Library and Web of Science databases. Only studies using the World Health Organization Quality of Life (WHOQOL) or its brief version or the Short Form-36 Health Survey (SF-36) were included. Fifteen case-control studies with 2195 schizophrenia subjects and 1508 healthy controls were included in this meta-analysis. The WHOQOL/WHOQOL-BREF score was significantly lower in physical health (SMD = -1.80, 95% CI: -2.31 to −1.28, P < 0.001), psychological health (SMD = -1.28, 95% CI: -1.72 to −0.83, P < 0.001), social relationships (SMD = -1.60, 95% CI: -2.05 to −1.15, P < 0.001), and environment domains (SMD = -0.98, 95% CI: -1.38 to −0.59, P < 0.001) in schizophrenia subjects compared to controls. The SF-36 score was significantly lower in both physical (SMD = -1.09, 95% CI: -1.41 to −0.76, P < 0.001 and mental health domains (SMD = -2.08, 95% CI: -3.58 to −0.59, P = 0.006) in schizophrenia subjects than in controls. Subgroup and meta-regression analyses found that age, male gender, illness duration and income have significant moderating effects on QOL. The meta-analysis of studies with standardized measures confirmed that QOL in schizophrenia subjects is significantly lower than healthy controls. Effective interventions should be developed to improve QOL for this population.