The aim of this study was to propose an index [Index of Biotic Integrity for the Río de la Plata (IBIRP)] formulated from a minimum of information-rich metrics related to biological integrity for evaluation of the coastal freshwater tidal zone of the Río de la Plata estuary. A total of 23 sites were selected along 170 km of shoreline (34°27′10″ S, 58°30′21″ W and 35°23′28″ S, 57°08′50″ W), being influenced by different land uses. We explored 36 biotic descriptors (designated candidate metrics), each of which is considered as an environmental indicator, and selected four metrics: two related to phytoplankton assemblage (planktonic cyanobacterial density and phytoplanktonic total density) and two linked to benthic assemblages, the diatoms (percent most tolerant taxa), and the invertebrates (percent Tanaidacea). The metrics that were chosen to integrate the IBIRP provide valuable information about the biotic integrity both in terms of time and space. The multimetric index can assume values between 0 (very bad status) and 10 (very good status). The IBIRP correlated significantly with the second (p < 0.001) and fourth (p < 0.01) factors of the factor analysis—those being related to variables indicative of eutrophication and organic pollution. This index constitutes an approach that is capable of reflecting the anthropogenic impacts produced along the coast of the Río de la Plata, with the inherent flexibility of being subject to modification and ultimate validation for estuaries of similar characteristics.