Transport of carbon, major and trace element by rivers in permafrost-affected regions is one of the key factor of circumpolar aquatic ecosystem response to climate warming and permafrost thaw. While seasonal and annual export fluxes (yields) of carbon (C) and inorganic solutes are fairly well known for all large Arctic rivers, spatial variations in elementary concentration along the river length and among its tributaries remain poorly understood. Moreover, the landscape factors controlling riverine element concentration in permafrost-affected regions are still poorly constrained. This is especially true for the largest river of Eastern Siberia, the Lena River, which drains through continuous permafrost zones with highly variable lithology and vegetation. Here we present the results of C, major and trace element measurements over a 2600-km transect of the Lena River main stem (upper and middle reaches) including its 30 tributaries, conducted at the peak of the spring flood. There were two main group of solutes in the main stem depending on their spatial pattern: i) elements that decreased their concentrations downstream, from SW to NE (Cl, SO4, DIC, Li, B, Na, Mg, K, Ca, As, Sr, Mo, Sb, Ba and U), which probably reflected a decrease in the proportion of carbonate rocks in the watershed and the degree of groundwater feeding, and ii) elements that increased their concentrations downstream (Al, Ti, Cr, Fe, Ga, Rb, Y, Zr, Nb, Cs, REEs, Hf and Th), which was tentatively linked to an increase in organic C stock in soils, larch forest coverage and enhanced mobilization of lithogenic elements from silicate soil minerals. Based on landscape parameters of Lena tributaries, we tested the impact of major environmental factors on major and trace element spatial pattern. Among all the variables, the proportion of sporadic permafrost on the watershed strongly controlled concentrations of soluble highly mobile elements (Cl, B, DIC, Li, Na, K, Mg, Ca, Sr, Mo, As and U). Another important factor of element concentration control in the Lena River tributaries was the coverage of watershed by light (B, Cl, Na, K, U) and deciduous (Fe, Ni, Zn, Ge, Rb, Zr, La, Th) needle-leaf forest (pine and larch). The latter, however, could also reflect the DOC-enhanced transport of low-soluble trace elements in the NW part of the basin. This part of the basin is dominated by silicate rocks and continuous permafrost, as compared to carbonate rock-dominated and groundwater-affected SW part of the Lena River basin. Overall, the impact of rock lithology and permafrost on major and trace solutes of the Lena River basin during the peak of spring flood was mostly detected at the scale of the main stem. Such an impact for tributaries was much less pronounced, because of the dominance of surface flow and lower hydrological connectivity with deep groundwater in the latter. Future changes in the river water chemistry linked to climate warming and permafrost thaw at the scale of the whole river basin are likely to be linked to changes in spatial pattern of dominant vegetation, rather than to the permafrost regime. We argue that comparable studies of large, permafrost-impacted rivers during most contrasting seasons, including winter baseflow, should allow efficient prediction of future changes in riverine ‘inorganic’ hydrochemistry induced by permafrost thaw.