Henderson Sandford was born around 1834 in Ireland to James and Elizabeth Sandford. His father was a farmer who owned $2,000 of real estate by 1850. The family eventually immigrated to America and settled in Rockbridge County, Virginia. His father died in 1855, and he helped care for his mother and siblings. By 1860, he was working as a farmer in Rockbridge County, and he owned $7,000 of real estate and $6,576 of personal property.
He enlisted in the Confederate army on March 19, 1862, and he mustered in as a sergeant in Company E of the 27th Virginia Infantry. The regiment took part in the Shenandoah Valley campaign of 1862. He was wounded in the Battle of Port Republic on June 9, 1862, and he spent the next several months recovering. It is unclear if he ever rejoined the regiment. He died at Buffalo Creek, Virginia, on February 15, 1867.