The isotopic composition of water is one of the main tools used to track the origin and pathways of moisture from source to precipitation site, and the recharge characteristics of groundwater and surface waters. Further, in order to asses the role of climate and regional physiographic characteristic of the Earth’s surface in determining the availability of water resources, dense networks long times series of δ¹⁸O and δ²H in precipitation and surface water are required. However, in many parts of the world, such data is lacking or has numerous gaps. In this context, we present a database of monthly δ¹⁸O and δ²H in precipitation (22 stations) and rivers (19 stations) in Romania and Republic of Moldova, spanning the period between January 2015 and December 2017. The dataset covers an area where multiple potential sources of moisture (Atlantic Ocean, Mediterranean, Black and Caspian Seas), complex surface topography and competing large-scale atmospheric circulation patterns result in highly complex conditions leading to precipitation and surface runoff generation. Our data shows that regional differences in the δ¹⁸O and δ²H of precipitation and rivers are linked to the blocking effect of the Carpathian Mountains and the interactions between different atmospheric circulation patterns: the North Atlantic Oscillation and the Siberian High (in winter), northward expanding Mediterranean cyclones (in autumn and winter), and long-lasting heat waves (in summer). δ¹⁸O and δ²H in rivers generally follow those in precipitation, but also reflect the strong evaporative conditions in the dry continental climate in summer and the effect of melt water from winter snow in spring. The data can offer a strong support for future studies aimed towards understanding the role of changing rainfall patterns, warming climate and reduced winter snow accumulation on water availability and stress in the region.