Bulow was born of German ancestry to Joseph and Elizabeth (Ebendorf) Bulow near Moscow in Clermont County, Ohio, where he was raised and educated. In 1893, he graduated with a law degree from the University of Michigan.

During 1893, Bulow moved to South Dakota. He resided in Sioux Falls, where he worked for the Joe Kirby office. Then, he came by horse and carriage to Beresford, where he set up his own law office and helped to develop the town. While residing in Beresford, Bulow spent twenty-five years as city attorney from 1902 to 1927, except while serving as mayor from 1912 to 1913. He also served as County Judge for Beresford in 1918. Bulow served as Governor of South Dakota from 1927 to 1931 and as a member of the US Senate from 1931 to 1943. During his entire life, Bulow kept a legal residence in Beresford, South Dakota and voted by absentee ballot. After his second term in the US Senate, William Bulow retired and spent the rest of his life residing at 3901 Connecticut Avenue NW in Washington, DC. Bulow spent his last few years in failing health and was blind during his last four years.

Beresford, South Dakota honored William J. Bulow during the town's seventy-five year jubilee observance in 1959. The city's park was dedicated as "Bulow Park" on June 3, 1959. Almost nine months later, Bulow died; and, his body was returned to Beresford for burial at the St. John Catholic Cemetery, where he was laid to rest next to his first wife, Katherine (Reedy) Bulow (January 29, 1875 - September 17, 1918). Years later, Bulow's house in Beresford, South Dakota was declared a historic landmark.