The estuaries and tidal rivers of the Gulf of Maine have rarely been surveyed systematically for marine mammals. We report here on three years of survey data, 2017 to 2019. This study employed a shipboard visual line-transect methodology study design, collecting data on marine mammals in the lower Piscataqua River, which is confluent with the Gulf of Maine. Marine mammal species observed most often were harbor seals (Phoca vitulina) and gray seals (Halichoerus grypus), with a resulting in-water density estimate of 1.02 seals/km2 and an abundance estimate of seven harbor seals and one gray seal (CV = 19.3%) in the survey area. Seals were present in all months of the year. No live pups were detected. Harbor porpoises (Phocoena phocoena) and minke whales (Balaenoptera acutorostrata) were also observed, but the sightings (6 harbor porpoises; 7 minke whales) did not yield enough data to estimate density or abundance. The minke whales were present during August and September 2018, concurrent with an influx of Atlantic menhaden (Brevoortia tyrannus), a prey species. The consistent albeit relatively low marine mammal species sightings and abundances suggest that the lower Piscataqua River is used regularly by a relatively small number of harbor and gray seals, although not for pupping, and occasionally by harbor porpoises and by foraging minke whales. This is the first study of its kind in an estuarine environment in the Gulf of Maine.