The area abounded in shellfish, striped bass, bluefish and swordfish and drew Indians as well as Europeans for offshore fishing as well as to the massive herring runs. Early settlers relied on agriculture, grazing and raising hay for cattle but the town grew very slowly. By 1700 there were only three families in Tisbury with a total of 27 people; in 1775 there were only 45 families with 225 people.

In 1787 there were 21 licensed inn holders, again clearly servicing a transient population much larger than the permanent one and certainly foreshadowing the town's modern character. Residents managed the port, fishing boats and salt works and the town built deep water wharves in 1836 as well as two marine railways to facilitate boat handling. The first submarine telegraph line was laid across Vineyard Sound to West Chop in 1856, significantly improving communications for townspeople.

Tisbury Mass is located in Located on the northernmost portion of Martha's Vineyard, an island 20 miles long and 10 miles wide situated five miles south of the southwest tip of Cape Cod. Tisbury is bordered by Vineyard Sound on the north, Oak Bluffs on the east and south, and West Tisbury on the west.