For many decades, prolificacy has been selected in meat sheep breeds as a polygenic trait but with limited genetic gain. However, the discovery of major genes affecting prolificacy has changed the way of selection for some ovine breeds implementing gene-assisted selection as in the French Lacaune and Grivette meat breeds, or in the Spanish Rasa Aragonesa breed. Based on statistical analysis of litter size parameters from 34 French meat sheep populations, we suspected the segregation of a mutation in a major gene affecting prolificacy in the Noire du Velay and in the Mouton Vendeen breeds exhibiting a very high variability of the litter size. After the genotyping of mutations known to be present in French sheep breeds, we discovered the segregation of the FecL(L) mutation at the B4GALNT2 locus and the FecX(Gr) mutation at the BMP15 locus in Noire du Velay and Mouton Vendeen, respectively. The frequency of ewes carrying FecL(L) in the Noire du Velay population was estimated at 21.2% and the Mouton Vendeen ewes carrying FecX(Gr) at 10.3%. The estimated mutated allele effect of FecL(L) and FecX(Gr) on litter size at + 0.4 and + 0.3 lamb per lambing in Noire du Velay and Mouton Vendeen, respectively. Due to the fairly high frequency and the rather strong effect of the FecL(L) and FecX(Gr) prolific alleles, specific management programmes including genotyping should be implemented for a breeding objective of prolificacy adapted to each of these breeds.