In 1887, Kress opened a stationery and notions store in Nanticoke, Pennsylvania. As the business prospered he used his profits to open additional stores, naming his chain “S. H. Kress & Co.” These eventually would become popularly known as the “Kress Five and Dime” stores. Unlike many businessmen of his day who only opened their stores in large urban areas, Kress wisely located his stores in smaller cities in 29 states he felt had growth potential. These stores became the jewel of many of these cities, which only had a dry goods or general store until then. By the mid-1920s, he was living in a penthouse at 1020 Fifth Avenue in New York City, across the street from the Metropolitan Museum of Art, which he visited and contributed to regularly.

S. H. Kress & Co., a chain of “five and dime” retail department stores, was started in Nanticoke, Pennsylvania, by Samuel H. Kress in 1896. Eventually expanding to over 200 locations nationwide, Kress stores were long a familiar sight in many cities and towns of the United States. The Kress chain was known for the fine architecture of the stores, with a number of locations being hailed by architects for their design. A number of former Kress stores, now put to other uses, are ranked as landmarks. Some of the most well-known Kress locations included New York City’s Fifth Avenue; Canal Street, New Orleans; and Hollywood’s Hollywood Boulevard. In 1964 ownership of Kress was acquired by Genesco, Inc. The company abandoned its center-city stores and moved to the shopping malls. Genesco began liquidating Kress and closing down the Kress stores in 1980.

Kress was founder and president of the eponymous Samuel H. Kress Foundation. An avid art lover, he acquired, through art dealer Joseph Duveen and with the advice of art historian William Suida , a collection of paintings and sculpture, primarily of the Italian Baroque school. Luckily for Kress, these paintings were thought to be “out of date” and “old fashioned” during the Victorian and Edwardian age, so he was able to purchase them at relatively low prices. In 1929 he gave the Italian government a large sum for the restoration of a number of architectural treasures in Italy. Beginning in the 1930s Kress decided to give much of his art collection to museums across the country while he was still alive. Many paintings were donated to the same smaller cities that had brought him his fortune with their stores. In several cases, his gifts became the founding basis for museums in those areas which otherwise could never have afforded artworks of such importance and quality.

On March 17, 1941, Kress and Paul Mellon gave a large gift of art to the people of the United States, thereby establishing the National Gallery of Art in Washington, D.C. Franklin D. Roosevelt accepted the gift personally.

Kress died in 1955 and is interred in the Woodlawn Cemetery in the Bronx, New York City.