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In 1955, Margaret and Philip Isely founded a door-to-door sales operation called the Builder's Foundation. The first store opened in 1958 in Denver, Colorado. The inspiration for the business came after the birth of their second child. Margaret became ill and found "conventional medicine" to be unhelpful to her. She treated herself using principles in Adelle Davis 's controversial book Let's Get Well.
In the 1960s, the Iselys converted a cottage-style house into a store, inspiring the name Vitamin Cottage. The store opened in Lakewood, Colorado, in 1963. In 1974, the second Vitamin Cottage location opened in Denver.
Natural Grocers founded a cycling team in 1987.
In 1995, the company name was briefly changed to Vitamin Cottage Natural Food Emporium.
Margaret Isely died in 1997, and the Iselys' children took over the business the following year.
In the 2010s, Natural Grocers stopped selling what they call "confinement dairy products", which includes milk from cows that aren't allowed to graze.
In 2026, the company opened its first location in Wisconsin.