Eckerd was founded in September 1898 by 27-year-old J. Milton Eckerd and Z. Tatom in Erie, Pennsylvania. In the company's early years, it operated at 1105 State Street in downtown Erie as the Erie Cut-Rate Medicine Store. In 1912, Eckerd and Tatom sold their original store to Eckerd's sons and moved to Wilmington, Delaware, establishing a new store. From Delaware, the chain expanded to North Carolina and later Florida. Jack Eckerd, son of the founder, was responsible for the expansion of the company when he acquired three stores in Florida in 1952.
In 1961, Eckerd changed from a proprietorship to a publicly owned company. At the height of Eckerd's success, it had over 2,800 stores in more than 20 states. Eckerd was the dominant drug chain in Florida, Texas, and Delaware.
In 1996, J.C. Penney and Eckerd agreed to merge. Under the agreement, all of JCPenney's Thrift Drug unit of drug stores (comprising Thrift Drug, Kerr Drugs, Fay's Drugs, and some Rite Aid stores) were rebranded to the larger Eckerd name. This marked Eckerd's re-entry into the Pennsylvania market. Eckerd was owned by JCPenney from 1997 to 2004, and was one of the largest drug store chains in the U.S. One carryover from the Thrift Drug days after the merger took over was the presence of JCPenney Catalog Centers inside certain locations, which enabled Eckerd customers to order merchandise from store catalogs and pick it up at an Eckerd location.
In 1998, Eckerd acquired the 141-store Genovese chain in the New York metropolitan area, and renamed the stores in 2003.
JCPenney, which had seen its seven-year ownership of Eckerd as a distraction that would cost too much to continue fixing, in March 2004 formally declared that it would carry Eckerd on its books as a discontinued asset. Penney took a $1.3-billion charge against earnings in connection with selling the drugstore chain that had been accounting for 45 percent of its annual revenues.
In July 2004, JC Penney sold all of the Eckerd stores along the Eastern Seaboard from Georgia to Connecticut to the Jean Coutu Group. The other stores, mainly in the Southeastern and Southwestern United States, were sold to CVS. The other Eckerd stores that were sold to the Jean Coutu Group were merged with Coutu's other American pharmacy chain, Brooks Pharmacy.