Thessaly, Central Greece, is an endemic area for leishmaniasis with higher incidence rate during the last years. We herein investigated the geographical distribution of human leishmaniasis cases and Leishmania infected dogs in relation to environmental parameters to identify high-risk areas. All the human leishmaniasis cases (n = 82) reported to Hellenic Centre for Disease Control and Prevention from 2007 to 2014 and 85 Leishmania polymerase chain reaction positive dogs were included in this study. To analyse the data geographical information system (GIS) together with the Ecological Niche Model (ENM) were used. The most important findings of the study were: (i) Central plain of Thessaly together with the coast line and the western and eastern lowlands were identified as high-risk geographical areas. (ii) The highest percentage of the high-risk areas was found in low altitude (<200 m above sea level) and in irrigated and cultivated agricultural areas. (iii) A total of 20% of the human settlements was found in high-risk areas. (iv) The maximum temperature of the warmest month contributes the highest per cent to define both environmental niche profiles for humans and dogs. (v) The ENM could be a useful tool for the epidemiological study of leishmaniasis. Spatial analysis may allow the design of entomological studies and identify target population in order to implement preventive measures.