In June 1810, Taylor married Margaret Mackall Smith, whom he had met the previous autumn in Louisville. "Peggy" Smith came from a prominent family of Maryland planters; she was the daughter of Major Walter Smith, who had served in the Revolutionary War. Zachary and Peggy had a total of six children:
Ann Margaret Mackall Taylor (1811–1875), married Robert C. Wood, a U.S. Army surgeon she had met while living Fort Snelling, in 1829.
Sarah Knox Taylor (1814–1835) married Jefferson Davis in 1835, whom she had met through her father at the end of the Black Hawk War; she died at 21 of malaria in St. Francisville, Louisiana, shortly after her marriage.
Octavia Pannill Taylor (1816–1820)
Margaret Smith Taylor (1819–1820),[6] died in infancy along with Octavia when the Taylor family was stricken with a "bilious fever"
Mary Elizabeth Taylor (1824–1909), married William Wallace Smith Bliss (died 1853) in 1848
Richard "Dick" Taylor (1826–1879),[6] Confederate Army general during the Civil War