Postglacial varved and rhythmically-laminated clays deposited during the transition from glacial Lake Vermont (LV) to the Champlain Sea (CS) record hydrological changes in the Champlain-St. Lawrence Valley (CSLV) at the onset of the Younger Dryas ∼13.1–12.9 ka linked to glacial lake drainage events. Oxygen isotope (δ18O) records of three species of benthic foraminifera (Cassidulina reniforme, Haynesina orbiculare, Islandiella helenae) from six sediment cores and the freshwater ostracode Candona from one core were studied. Results show six large isotope excursions (∼0.5 to >2‰) in C. reniforme δ18O values, five excursions in H. orbiculare (<0.5 to ∼1.8‰), and five smaller changes in I. helenae (<0.5‰). δ18O values in Candona show a 1.5–2‰ increase in the same interval. These isotopic excursions in co-occurring marine and freshwater species in varve-like sediments indicate complex hydrological changes in the earliest Champlain Sea, including brief (sub-annual) periods of complete freshening. One hypothesis to explain these results is that multiple abrupt freshwater influx events caused surface-to-bottom freshening of the Champlain Sea over days to weeks. The most likely source of freshwater would have been drainage of the Morehead Phase of glacial Lake Agassiz, perhaps in a series of floods, ultimately draining out the St. Lawrence Estuary.