George Clinton Murphy worked as a buyer for the Johnstown, Pennsylvania J.G. McCrory store. He resigned his position in 1906 and opened the first G.C. Murphy 5 & dime in McKeesport, Pennsylvania.

By the mid-20th century there were "Murphy's" locations in twenty-three states. The chain was the first 5 & 10 to market itself with television commercials. In 1955, a shift to suburban shopping center stores began, with new locations in Erie and Brentwood, Pennsylvania.

The company followed the lead of Kresge and Woolworth by opening its own discount-mart-type operation. Known as Murphy's Mart, the chain debuted in Bethel Park, Pennsylvania May 27, 1970.

The 5 & 10 and Murphy's Mart divisions were sold to Connecticut-based Ames in August 1985, with Murphy's Mart stores being rebranded as Ames locations in 1986. The 5 & 10-type stores continued to operate under the Murphy's banner.

Ames sold all Murphy's mercantiles to McCrory Stores in August 1989. Like Ames, they retained the Murphy's banner. With the dissolution of McCrory Stores, in early 2002, the last G.C. Murphy stores were shuttered.