This study evaluated the effects of three genomic indicators of heterosis on female fertility and lifetime productivity, and quantified changes over 11 production cycles in a crossbred cow herd. Pedigree-based breed composition (pBC) was determined and used to calculate retained heterozygosity for 412 replacement heifers born from 2004 to 2014 at the Lacombe Research and Development Centre (AB, Canada). Heifers were followed as cows over 1050 mating opportunities, 11 production cycles, and five parities. Heifers and their sires (51) were genotyped and these genotypes were used to predict each animal’s genomic breed composition (gBC) and three genomic indicators of heterosis: (1) retained heterozygosity (RHETg), (2) heterozygous proportion (H), and (3) retained heterosis (RHg). Correlations between pedigree and genomic breed fractions for Angus, Hereford, and Charolais were high (rp = 0.74–0.94; P < 0.001). Genomic indicators of heterosis were highly related (rp = 0.61 for RHETg vs. H; 0.71 for RHg vs. H; 0.96 for RHETg vs. RHg; P < 0.001). Each 10% change in RHETg resulted in 51 ± 20 d longer survival (P = 0.011) in the herd and 35.7 ± 15.2 kg more (P = 0.019) calf wean weight per cow exposed to breeding when summed over five parities. These differences resulted in an extra $161 per heifer in a year. Optimizing heterosis using genomic tools can be very beneficial for the cow herd if applied correctly.