The study focuses on the probabilistic seismic risk assessment of earthquake prone old urban centers. This issue becomes even more complex if the considered area is a highly populated, cultural or commercial center. Hence it is an important task to estimate regional earthquake losses and to develop strategies for earthquake mitigation through seismic risk prioritization among such vulnerable populated old urban areas. For this purpose, a subdistrict with six neighborhoods in Beyoglu, Istanbul has been selected as the study area, which is located in a high-seismicity region. This is one of the most attractive cultural places in the city as well as a commercial center with a high population. Building stock is dense and composed of many old and deficient buildings located within close vicinity of active faults. For risk assessment, site-specific hazard curves are obtained first. Then reinforced concrete and masonry buildings in the region are classified by using the results of a recent walk down survey data and fragility curve sets that reflect local structural characteristics of the buildings in the area are attained to each class. In the last step, probabilistic seismic risk assessment approach is utilized to obtain the estimated damage state distributions at the considered neighborhoods for a 50-year time interval. The results reveal the urgency in order to take precautions to mitigate earthquake losses in vulnerable old urban centers. This study is deemed to propose a potential approach by carrying out site-specific hazard, vulnerability and risk assessments as an assistance to risk mitigation efforts.