Seawater warming is impacting marine ecosystems, but proper evaluation of change requires the availability of long-term biological data series. Mesco Reef (Ligurian Sea, Italy) offers one of the longest Mediterranean data series on sessile epibenthic communities, based on underwater photographic surveys. Photographs taken in four stations between 20 m and 40 m depth allowed calculating the percent cover of conspicuous species in 1961, 1990, 1996, 2008, and 2017. Multivariate analysis evidenced an abrupt compositional change between 1990 and 1996. A parallel change was observed in Ligurian Sea temperatures. Two invasive macroalgae (Caulerpa cylindracea and Womersleyella setacea) became dominant after 1996. Community diversity was low in 1961 to 1996, rapidly increased between 1996 and 2008, and exhibited distinctly higher values in 2008–2017. A novel community emerged from the climate shift of the 1990s, with many once characteristic species lost, reduced complexity, biotic homogenization, greater diversity and domination by aliens. Only continued monitoring will help envisage the possibility for a reversal of the present phase shift or for further transformations driven by global change.