Seymour attended the district school and at fifteen, though he had never gone to high school, began to teach school himself. At seventeen he moved to Hart, Michigan, where for a few years he worked as a salesclerk. Then he left for Reading where in partnership with his first cousin, Frank W Woolworth, he opened a five-and-ten-cent store which failed. Unfazed, young Knox established the same kind of operation in Newark, New Jersey This succeeded, but Knox once again sold out and with Woolworth formed Woolworth & Knox in Erie.

With success here, Knox came to Buffalo in 1890 where he opened two stores, one on Main, the other on William Street, to be known as S. H. Knox. Woolworth expanded his empire by using partners to organize single outlets. Thus he could minimize his own outlay. In 1912, however, he merged his rivals, including S. H. Knox, into a company, which in time boasted 596 stores worldwide. Its headquarters were in the Woolworth Building, a $13 million skyscraper on lower Broadway in New York built in 1913. The new company, E W Woolworth, was capitalized at $65 million. Besides his large holdings in this gigantic venture, Knox was made first vice-president. He had also become a heavy player in the affairs of Marine National by purchasing Stephen Clement's interest in 1913.

Knox was married in June 1890, the year he came to Buffalo. According to an article in the Buffalo Evening News,

Mrs. Knox was the former Grace Millard of Detroit, the daughter of Charles and Sarah Avery Millard .... To some of her friends, Mrs. Knox confided the story of her romance with the young man with whom she was to rise to riches. She recalled to these friends that a trip to Buffalo brought about her meeting with Mr. Knox. She was one of a party of girls who came here on a short vacation, one of the girls knew Mr. Knox and he entertained the group.

Especially attracted to Grace Millard, he saw her frequently during her stay here and it wasn't long after the visit that they were married in Detroit and returned here to make their home. Her parents followed, arriving here shortly before Mr. Knox opened his first Buffalo store in the old Palace Arcade near Lafayette Square in the early 1880s [read 1890s. -- Buffalo Evening News, August 31, 1936

The newlyweds' first home was #414 Porter Avenue; by 1896 they were at #467 Linwood (PHOTO)