Marine cyanobacteria depend on light for photosynthesis, restricting their growth to the photic zone. The upper part of this layer is exposed to strong UV radiation (UVR), a DNA mutagen that can harm these microorganisms. To thrive in UVR-rich waters, marine cyanobacteria employ photoprotection strategies that are still not well defined. Among these are photolyases, light-activated enzymes that repair DNA dimers generated by UVR. Our analysis of genomes of 81 strains of Synechococcus, Cyanobium, and Prochlorococcus isolated from the world’s oceans shows that they possess up to five genes encoding different members of the photolyase/cryptochrome family, including a photolyase with a novel domain arrangement encoded by either one or two separate genes. We disrupted the putative photolyase-encoding genes in Synechococcus sp. strain RS9916 and discovered that each gene contributes to the overall capacity of this organism to survive UVR. Additionally, each conferred increased survival after UVR exposure when transformed into Escherichia coli lacking its photolyase and SOS response. Our results provide the first evidence that this large set of photolyases endows Synechococcus with UVR resistance that is far superior to that of E. coli, but that, unlike for E. coli, these photolyases provide Synechococcus with the vast majority of its UVR tolerance.