Sexual selection is widely appreciated for generating remarkable phenotypic diversity, but its contribution to adaptation and the purging of deleterious mutations is unresolved. To provide insight into the impact of sexual selection on naturally segregating polymorphisms across the genome, we previously evolved 12 populations of Drosophila serrata in a novel environment employing a factorial manipulation of the opportunities for natural and sexual selection. Here, we genotype more than 1,400 SNPs in the evolved populations and reveal that sexual selection affected many of the same genomic regions as natural selection, aligning with it as often as opposing it. Intriguingly, more than half of the 80 SNPs showing treatment effects revealed an interaction between natural and sexual selection. For these SNPs, while sexual selection alone often caused a change in allele frequency in the same direction as natural selection alone, when natural and sexual selection occurred together, changes in allele frequency were greatly reduced or even reversed. This suggests an antagonism between natural and sexual selection arising from male-induced harm to females. Behavioral experiments showed that males preferentially courted and mated with high-fitness females, and that the harm associated with this increased male attention eliminated the female fitness advantage. During our experiment, females carrying otherwise adaptive alleles may therefore have disproportionally suffered male-induced harm due to their increased sexual attractiveness. These results suggest that a class of otherwise adaptive mutations may not contribute to adaptation when mating systems involve sexual conflict and male mate preferences.