During the planning of an urban environment, usually only economic and social parameters are taken into account. As a result, urban areas are susceptible to natural disasters, which cause extensive damages in them, because the cities or towns have been repeatedly located in vulnerable areas. In this study, for the protection of human environment, is proposed a unique approach of urban planning and sustainable development. The study area is Trikala Prefecture (Western Thessaly, Central Greece). An integrated evaluation of the suitable areas for urban growth and light industry development is proposed by using mainly natural hazards as well as geological–geomorphological–geographical characteristics of the study area. The used parameters were correlated by using the analytical hierarchical process (AHP) method and incorporated into a geographic information system (GIS) in order to produce the corresponding suitability maps. The study area is classified in five categories of very high, high, moderate, low, and very low suitability for urban growth and industrial development. Moreover, the spatio-temporal changes of the urban limits are studied since 1885 for the three major towns (Trikala, Kalambaka and Pyli) of the study area. These changes sketch out the urban growth trend. The comparison between the urban growth trend with the potential suitability for urban growth and industrial development of these towns lead to discrepancies. These can be attributed mainly to the fact that in the majority of cases, only geographical, social, and economical factors were used for urban development, whereas in our study, natural hazards, geomorphological, and geographical parameters were quantified and taken into account.