The town long focused on logging and sawmilling. It was platted as Gloversville on July 30, 1897 by H. C. Glover on whose homestead it was located. On June 29, 1899, the town was re-platted by Amanda B. Burger as Twisp. The name is a modification of the Native American word T-wapsp, the meaning of which is not known.

In Twisp the Twisp River, fresh from the Cascades, joins the Methow River. Left from Twisp, Twisp River Road leads into the Twisp River Valley, at the west end of which an extension, through Twisp Pass and Cascade Pass, give the Methow Valley a direct link with Puget Sound and western Washington points.