Satellite DNA spans megabases of eukaryotic genome sequence. These vast stretches of tandem DNA repeats undergo high rates of sequence turnover, resulting in radically different satellite DNA landscapes between closely related species. Such extreme evolutionary plasticity suggests that satellite DNA accumulates mutations with no functional consequence. Paradoxically, satellite-rich genomic regions support essential, conserved nuclear processes, including chromosome segregation, dosage compensation, and nuclear structure. A leading resolution to this paradox is that deleterious alterations to satellite DNA trigger adaptive evolution of chromatin proteins to preserve these essential functions. Here we experimentally test this model of coevolution between chromatin proteins and DNA satellites by conducting an evolution-guided manipulation of both protein and satellite. We focused on an adaptively evolving, ovary-enriched chromatin protein, called Maternal Haploid (MH) from Drosophila. MH co-localizes with an 11 Mb 359-bp satellite array present in Drosophila melanogaster but absent in its sister species, D. simulans. Using CRISPR/Cas9-mediated transgenesis, we swapped the D. simulans version of MH into D. melanogaster. We discovered that D. melanogaster females encoding only the D. simulans mh (mh[sim]) do not phenocopy the mh null mutation. Instead, MH[sim] is toxic to D. melanogaster ovaries: we observed elevated ovarian cell death, reduced ovary size, and subfertility in mh[sim] females. Using both cell biological and genetic approaches, we demonstrate that MH[sim] poisons oogenesis through a DNA damage pathway. Remarkably, deleting the D. melanogaster-specific 359 satellite array from mh[sim] females completely restores female germline genome integrity and fertility. This genetic rescue offers experimental evidence that rapid evolution resulted in a cross-species incompatibility between the 359 satellite and MH. These data suggest that coevolution between ostensibly inert repetitive DNA and essential chromatin proteins preserves germline genome integrity.