The name Grisslehamn was first mentioned in a document from 1376 about the mail route between Sweden and Finland. This Grisslehamn was located some 20 km south of today's location. In the mid-18th century, most of the old village was destroyed in a fire, and it was decided to move Grisslehamn to its current location to make the mail route shorter. Conveying mail by row boat from Sweden to Åland, from whence it was transported to the Finnish mainland, was, together with fishing, one of the most important sources of income for the inhabitants of Grisslehamn and other parts of Roslagen for a long time, until steam ships took over the mail routes in the early 20th century.
The artist Albert Engström had a studio in Grisslehamn, where he painted oils and water colours of the Roslagen landscape. He lived in the town for a number of years, and his home is now a museum of his life and work.