Paleoclimate reconstructions are increasingly used to characterize climate variability and change prior to the instrumental record, in order to improve our estimates of climate extremes and to provide a baseline for climate change projections. Most of these reconstructions are focused on temperature, precipitation, and/or drought indices and, to a lesser extent, reconstruct streamflow variability. In this study, the first regional tree-ring width chronology (i.e. Quercus sp.), from the Caraorman forest (Danube Delta, Romania), was used to reconstruct the last ∼250 years of annual (from November previous year to July of the current year) streamflow of the Lower Danube River. The obtained results indicate a stable and significant correlation between the tree-ring width index from the Caraorman forest and the Danube streamflow at the Ceatal Izmail hydrologic station situated in the southeastern part of Europe. Interannual streamflow variation for the analyzed period indicates 14 extremely high flow years, with streamflow greater than 8780 m3/s (1770, 1771, 1799, 1836, 1838, 1839, 1871, 1876, 1877, 1879, 1940, 1941, 1997 and 2010) and 14 extremely low flow years, with streamflow lower than 5300 m3/s (1741, 1745, 1750, 1753, 1773, 1794, 1812, 1832, 1843, 1882, 1899, 1921, 1964 and 1994). Periods characterized by pluvials in the lower Danube Delta are associated with a low-pressure system centered over Europe, positive sea surface temperature (SST) anomalies over the Atlantic Ocean, and negative SST anomalies over the Baltic, North, and Mediterranean Seas. These large-scale conditions favor the advection of moist air from the Mediterranean and the Black Sea towards the southeastern part of Romania, which in turn leads to high precipitation rates over this region. Opposite to this, low streamflow years are associated with a high-pressure system centered over Europe, characterized by a northward shift of the storm tracks and negative SST anomalies over the Atlantic Ocean, and positive SST anomalies over the Baltic, North, and Mediterranean Seas. Based on our results, we argue that the reconstruction of river streamflow data based on the tree-ring width has important scientific and practical implications for a better understanding of the streamflow variation of the past, necessary for water resource management and environmental-hydrological protection.