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Sexual minority individuals experience higher rates of mental health problems than heterosexual people. It has been suggested that minority stress explains this disparity, partly by elevating rates of general psychological risk factors such as low self-esteem. This study investigated self-esteem in sexual minority people compared with heterosexual people through a systematic review and meta-analysis. A systematic search of four databases was conducted. Observational studies comparing self-esteem in sexual minority and heterosexual men and women separately were included. A qualitative synthesis and random effects meta-analysis were conducted. Potential moderators were explored using subgroup analyses of age, sexual minority orientation, and sample type. Thirty-two eligible studies were identified; 25 compared self-esteem in men and 19 in women. Most studies used the Rosenberg Self-Esteem Scale (RSES) to measure self-esteem. Compared with heterosexual men and women, there was significantly lower self-esteem in sexual minority men (SMD = −0.33, 95% CI [−0.44, −0.23]) and women (SMD = −0.20, 95% CI [−0.29, −0.11]). This difference appeared to be moderated by sample type: There was preliminary evidence for more robust differences in men and bisexual individuals. Findings are consistent with the suggestion that self-esteem is lower in sexual minorities than in heterosexual individuals. However, caution is required in drawing firm conclusions due to methodological limitations of the included studies. Self-esteem is a potential target for intervention to prevent psychological disorders in this population.