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Objective To evaluate the association between cleft lip and/or cleft palate (CL/P) and breastfeeding (BF). Design A systematic review and meta-analysis were performed based on studies published in PubMed, Scopus, Web of Science, Cochrane Library, LILACS, BBO, and Embase databases, and in the gray literature. The search occurred in September 2021 and was updated in March 2022. Observational studies evaluating the association between BF and CL/P were included. Risk of bias was analyzed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was conducted. Certainty of evidence was evaluated using the GRADE approach. Main Outcome Measure(s) Frequency of BF in relation to the presence or absence of CL/P, as well as to the type of CL/P. The association between cleft type and BF challenges was also evaluated. Results From a total of 6863 studies identified, 29 were included in the qualitative review. Risk of bias was moderate and high in most studies (n = 26). There was a significant association between the presence of CL/P and absence of BF (OR = 18.08; 95% CI 7.09–46.09). Individuals with cleft palate with or without cleft lip (CP ± L) had a significantly lower frequency of BF (OR = 5.93; 95% CI 4.30–8.16) and a significantly higher frequency of BF challenges (OR = 13.55; 95% CI 4.91–37.43) compared to individuals with CL. Certainty of the evidence was low or very low in all analyses. Conclusion The presence of clefts, especially those with palate involvement, is associated with higher chances of absence of BF.