In 1765, the first wave of colonization occurred as a result of the Great Upheaval when Acadians from Boston arrived and settled on the south bank of the Vacher Creek (French: ruisseau Vacher) in the Seignory of Saint-Sulpice. The settlement was called Bas-du-Ruisseau-Vacher (meaning "Lower Vacher Creek"), named after a certain Vacher who accompanied surveyor John Péladeau in 1767 on the seignory's territory. In 1790, the settlement grew when families from Château-Richer arrived. Actual clearing of the area began around 1820.[5]
In March 1883, Sainte-Marie-Salomé became home to the second creamery of Quebec.[5]
In 1888, the parish municipality of Sainte-Marie-Salomé was established by separating from Saint-Jacques-de-l'Achigan, and named after Mary Salome. Its letters patent used the misspelled "Salomée", which was not corrected until 1986. In 1889, the local post office opened. During the 1890s, the location was also known as Sainte-Marie-Salomé-de-Port-Royal, indicating the origin of its Acadian settlers.[5]