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A systematic review of studies in humans was conducted to update evidence on the association between the amount of sugars intake and dental caries and on the effect of restricting sugars intake to < 10% and < 5% energy (E) on caries to inform the updating of World Health Organization guidelines on sugars consumption. Data sources included MEDLINE, EMBASE, Cochrane Database, Cochrane Central Register of Controlled Trials, Latin American and Caribbean Health Sciences, China National Knowledge Infrastructure, Wanfang, and South African Department of Health. Eligible studies reported the absolute amount of sugars and dental caries, measured as prevalence, incidence, or severity. The review was conducted and reported in accordance with the PRISMA statement, and the evidence was assessed according to GRADE Working Group guidelines. From 5,990 papers identified, 55 studies were eligible - 3 intervention, 8 cohort, 20 population, and 24 cross-sectional. Data variability limited meta-analysis. Of the studies, 42 out of 50 of those in children and 5 out of 5 in adults reported at least one positive association between sugars and caries. There is evidence of moderate quality showing that caries is lower when free-sugars intake is < 10% E. With the < 5% E cut-off, a significant relationship was observed, but the evidence was judged to be of very low quality. The findings are relevant to minimizing caries risk throughout the life course.