The late persistence in Southern Iberia of a Neandertal-associated Middle Paleolithic is supported by the archeological stratigraphy and the radiocarbon and luminescence dating of three newly excavated localities in the Mula basin of Murcia (Spain). At Cueva Antón, Mousterian layer I-k can be no more than 37,100 years-old. At La Boja, the basal Aurignacian can be no less than 36,500 years-old. The regional Middle-to-Upper Paleolithic transition process is thereby bounded to the first half of the 37th millennium Before Present, in agreement with evidence from Andalusia, Gibraltar and Portugal. This chronology represents a lag of minimally 3000 years with the rest of Europe, where that transition and the associated process of Neandertal/modern human admixture took place between 40,000 and 42,000 years ago. The lag implies the presence of an effective barrier to migration and diffusion across the Ebro river depression, which, based on available paleoenvironmental indicators, would at that time have represented a major biogeographical divide. In addition, (a) the Phlegraean Fields caldera explosion, which occurred 39,850 years ago, would have stalled the Neandertal/modern human admixture front because of the population sink it generated in Central and Eastern Europe, and (b) the long period of ameliorated climate that came soon after (Greenland Interstadial 8, during which forests underwent a marked expansion in Iberian regions south of 40°N) would have enhanced the 'Ebro Frontier' effect. These findings have two broader paleoanthropological implications: firstly, that, below the Ebro, the archeological record made prior to 37,000 years ago must be attributed, in all its aspects and components, to the Neandertals (or their ancestors); secondly, that modern human emergence is best seen as an uneven, punctuated process during which long-lasting barriers to gene flow and cultural diffusion could have existed across rather short distances, with attendant consequences for ancient genetics and models of human population history.