In 1892, W. D. Byron & Sons opened a tannery in Mercersburg, Pennsylvania, and in 1897 opened a second location on the Conococheague Creek at Williamsport, Maryland. William's youngest son, Harold "Harry" Winchester Byron, took over operations of the Mercersburg tannery in 1901. The Byron's Mercersburg tannery was sold out of the family in 1945 due to lingering financial difficulties from the Great Depression, and the Byron estate in Mercersburg eventually left the family and became the Mercersburg Inn.
The plant at Williamsport suffered a fire caused by a lightning strike in 1903 that caused significant damage to buildings and stock, but the business rebounded quickly. In 1911, the Byron family opened a shoe manufacturing plant in Hagerstown, Maryland, called the Hagerstown Shoe & Legging Company. William's sons, Lewis T. (1870-1922) and Joseph Charles Byron (1860-1932), were the first two presidents of this shoe company. W. D. Byron & Sons remained in the family for three more generations, with William's son Joseph Charles Byron passing the torch to his son William Devereux II, and finally to the last president James "Jamie" Edgar Byron, the second of William Devereux Byron's great-grandsons. In 1976, after declaring bankruptcy due to the expense of switching from coal to oil and building facilities for processing waste materials, Garden State Tanning purchased W. D. Byron & Sons.