Reproduction among related individuals is generally maladaptive. Inbreeding imposes significant costs on individual reproductive success, and can decrease population fitness. Theory predicts that polyandrous females can avoid inbreeding by exploiting paternity-biasing mechanisms that enable differential sperm ‘use’. Evidence of sperm selection is difficult to demonstrate because patterns of non-random paternity can be generated by a variety of different mechanisms. Here, using competitive in vitro fertilisation in mice, we provide unequivocal evidence of sperm selection at the gametic level. We competed the sperm of sibling and unrelated males, and observed a fertilization bias toward the sperm of unrelated males. We standardised the number of competing sperm within each assay, so that our result can only be ascribed to ova-driven sperm selection against related sperm. We suggest that the expression of the paternal genotype on the sperm surface could provide the molecular basis for this mechanism of cryptic female choice. It is likely that the differential fertilization success of sibling versus non-sibling sperm translates to a paternity skew within litters at birth, which we had previously shown in house mice. We therefore provide evidence that female house mice benefit can from polyandry by avoiding fertilizations by genetically incompatible males, which also has important fitness implications for populations on the whole.