Leishmania infantum—the causal agent of human and canine leishmaniasis in the Mediterranean basin-remains the most important of the phlebotomine sand fly-borne pathogens in the area. However, information on phlebotomine sand flies in certain European regions remains scarce and consequently epidemiological modeling, risk prediction, and disease control are difficult. Thus, we aimed to investigate the presence and distribution of phlebotomine sand fly vectors of L. infantum in an endemic region of continental Mediterranean Spain. Climatically stratified trapping of phlebotomine sand flies was performed over 39 points in south- central Spain. Later on, the effect of ecogeographical variables—geography trend, climate, habitat, and hosts—over the abundance of the predominant species—Phlebotomus perniciosus Newstead, 1911—was analyzed. Polymerase chain reaction was performed over pools of the captured species to search for L. infantum DNA. There were 152 phlebotomine sand flies (142 Ph. perniciosus and 10 Phlebotomus ariasi Tonnoir, 1921) captured. Model results showed that Ph. perniciosus abundance is expected to be higher in warm agricultural areas within the study region in agreement to previous findings in other climatic regions. Molecular analyses revealed the presence of L. infantum DNA in pools from locations in the study region displaying the highest abundance of phlebotomine sand flies. These findings suggest that along mainland Spain, warm agricultural landscapes are more prone to harbor higher abundances of Ph. perniciosus and account for a higher risk of exposure to L. infantum.