<b><i>Background:</i></b> Sarcopenia can predispose individuals to falls, fractures, hospitalization, and mortality. The prevalence of sarcopenia depends on the population studied and the definition used for the diagnosis. <b><i>Objective:</i></b> This systematic review and meta-analysis aimed to investigate the association between sarcopenia and mortality and if it is dependent on the population and sarcopenia definition. <b><i>Methods:</i></b> A systematic search was conducted in MEDLINE, EMBASE, and Cochrane from 1 January 2010 to 6 April 2020 for articles relating to sarcopenia and mortality. Articles were included if they met the following criteria – cohorts with a mean or median age ≥18 years and either of the following sarcopenia definitions: Asian Working Group for Sarcopenia (AWGS and AWGS2019), European Working Group on Sarcopenia in Older People (EWGSOP and EWGSOP2), Foundation for the National Institutes of Health (FNIH), International Working Group for Sarcopenia (IWGS), or Sarcopenia Definition and Outcomes Consortium (SDOC). Hazard ratios (HR) and odds ratios (OR) were pooled separately in meta-analyses using a random-effects model, stratified by population (community-dwelling adults, outpatients, inpatients, and nursing home residents). Subgroup analyses were performed for sarcopenia definition and follow-up period. <b><i>Results:</i></b> Out of 3,025 articles, 57 articles were included in the systematic review and 56 in the meta-analysis (42,108 participants, mean age of 49.4 ± 11.7 to 86.6 ± 1.0 years, 40.3% females). Overall, sarcopenia was associated with a significantly higher risk of mortality (HR: 2.00 [95% CI: 1.71, 2.34]; OR: 2.35 [95% CI: 1.64, 3.37]), which was independent of population, sarcopenia definition, and follow-up period in subgroup analyses. <b><i>Conclusions:</i></b> Sarcopenia is associated with a significantly higher risk of mortality, independent of population and sarcopenia definition, which highlights the need for screening and early diagnosis in all populations.