Large-scale environmental patterns in the Humboldt Current System (HCS) deeply change during El Niño episodes, leading to the mass mortality of dominant species in coastal ecosystems. Here we explore how temperature and salinity changes affect life-history traits of the surf clam Mesodesma donacium. Growth and mortality rates under normal temperature and salinity were compared to those under anomalous (El Niño) higher temperature and reduced salinity. Moreover, the reproductive spatial-temporal patterns along the distribution range were studied and their relationship to large-scale temperature and salinity variability was assessed. M. donacium is highly sensitive to temperature changes, suggesting that the northward distribution is limited by high sea surface temperature. In contrast, this clam, particularly juveniles, was remarkably tolerant to low salinity, which may allow the spat to select river mouths as suitable areas for recruitment. Strong freshwater-input seasonality was found to best explain general patterns in the reproductive cycle and some local departures. Reported for the first time for the HCS, submarine groundwater discharge may act as steeping stone areas in the Atacama Desert coast, replacing the effect of river discharge in M. donacium populations. Owing to its narrow thermal tolerance, the expansion and dominance of M. donacium from the Pliocene/Pleistocene transition until present seems closely linked to the establishment and development of the cold HCS. Therefore, the recurrence of warming events (particularly El Niño since at least the Holocene) has submitted this cold-water species to a continuous extinction-recolonization process, in which thermal and osmotic tolerances play a key role.