The Arno River Basin is the second largest catchment in central Italy with a drainage area of 8,228 km². A total of 33 stream sediment samples of the Arno river, and its main tributaries, were analyzed to characterize its geochemical landscape. Major and trace elements’ geochemistry was examined and the magnetic susceptibility was measured to detect metallic anomalies. The obtained data were analyzed using the Compositional Data Analysis approach by combining Robust Factor Analysis with the calculation of the Robust Mahalanobis distance, which have proven to be effective tools to explain compositional changes throughout the basin. The investigated stream sediment data correlate well with the major geological units, but certain locations are affected by anthropogenic contaminations. The stream sediment composition of the upper reaches is mainly determined by the weathering of the bedrock. Major changes are observed in the Chiana valley, where industrial and agricultural activities are considered to be significant sources of contaminants. The rivers Era, Greve, Pesa, Elsa, Egola and Era around and downstream Florence, are mainly influenced by the weathering of ophiolitic rocks and to a minor extent by carbonates. P and Cu anomalies, resulting from industrial settlements and horticulture (flower and plant gardens), characterize the Ombrone, Bisenzio and Usciana rivers. Overall, stream sediments of tributaries are more affected by compositional changes than those of the main course, suggesting the Arno river sediments to be more resilient to geochemical threats.