Jellyfish are attractive biological indicators of shifts in the marine environment, as they have limited mobility and they are highly exposed to the physics and chemistry of the water column. For this study, we focused on three Mediterranean macro-jellyfish - Rhizostoma pulmo, Aurelia sp. and Phyllorhiza punctata. We used comparative genomics and molecular clock (timetree) approaches to estimate occurrences of past geological events and contemporary anthropogenic effects in the Mediterranean Sea. Our results proved that these events have left their mark on the genomes of marine jellyfish. Genomic data of R. pulmo revealed a divergence point between the East and West MS populations that occurred 4.59 Ma, after the Zanclean flood, suggesting that at this time these regions had formed the two distinct ecological environments we know today. We propose that before that time (4.59 Ma), the highly mixed Atlantic and Mediterranean waters led to the wide dispersal of different species in the MS, including the ancestral R. pulmo. At 4.59 Ma, a marine barrier between the Western and Eastern MS formed, indicating the possibility of a dramatic environmental event. The Central and Western MS showed signs of separation processes only at much later stages and at much slower rates. Using comparative genomics of the Aurelia species, we examined contemporary anthropogenic impacts with a focus on migration of scyphozoa across the Suez Canal (Lessepsian migration). Aurelia sp. is among the few scyphozoa we find in both seas. DNA analysis revealed that the Red Sea Aurelia sp. is more related to the Pacific Ocean Aurelia sp. than to the Eastern MS Aurelia species, while the latter is closer to populations from Croatia and Slovenia. Therefore, we conclude that there was no Lessepsian migration of the Aurelia species. Data from P. punctata showed that this species was only recently introduced to the MS, as samples from the MS were closer to Australian populations while they were distant from Mexico and Thailand populations. The recent introduction of P. punctata, apparently, results from anthropogenic transportation activity, such as ballast water discharge, with a known migration vector from Australia to the MS. Our findings demonstrate that jellyfish genomes can be used as a phylogeographic molecular tool to trace back past events across large temporal scales and reveal invasive species introduction due to human activity.