Spatial and temporal variability of the transformation of dissolved matter runoff in the Mezen’ River estuary is studied by results of the complex hydrological-hydrochemical researches lead in 2009 and 2015. The conservative behavior of major ions and dissolved forms of Li, Rb, Cs, Sr, B, F, As, Sb, and Mo is demonstrated. The additional input into solution reaching 93 and 32–38% of content in the river water mass is determined for phosphates and silicon. This is caused, apparently, by mobilization of these nutrients from pore waters of regularly tide-stirred bottom sediments and vertical mixing of the water column. The desorption flux of barium and uranium due to long-term interaction of terrigenic material with saline waters exceeded their input with a continental runoff reaching 180–380 and 90–150% of content of these elements in the river waters. Up to 50, 43, 29, 32, 44, 50, and 45% of Fe, Pb, Y, La, Ce, Pr, and Nd supplying with river runoff which are present in the form of strong organic complexes are removed from solution at the beginning of the mixing zone due to coagulation of colloids. It is drawn a conclusion on spatial homogeneity and long-term stability of transformation features of dissolved matter runoff in the Mezen’ River estuary. Peculiar characteristic of migration of dissolved phosphates, silicon, barium, and uranium are caused by hydrological features of the estuary.