He established a medical practice in Kentucky where he married a Methodist widow named Wolfe. Along with her two daughters they moved to Louisiana. In 1855 his wife gave birth to their daughter Cora. By 1861, Wirz had a successful medical practice.
In February, 1864, the Confederate government established Camp Sumter, a large military prison near the small railroad depot of Andersonville, Georgia, to house Union prisoners of war. In March, Wirz took command of Camp Sumter where he remained for over a year.
Though wooden barracks were originally planned, the Confederates incarcerated the prisoners in a vast, rectangular, open-air stockade originally encompassing sixteen and a half acres, which had been intended as only a temporary facility pending prisoner exchanges with the north. The prison suffered an extreme lack of food, tools and medical supplies, severe overcrowding, poor sanitary conditions and a lack of potable water. At its peak in August 1864, the camp held approximately 32,000 Union prisoners, making it the fifth largest city in the Confederacy. The monthly mortality rate from disease and malnutrition reached 3000. Around 45,000 prisoners were incarcerated during the camp's 14-month existence, of whom 13,000 (28%) died.
Wirz was arrested in May, 1865 by a contingent of federal cavalry and taken by rail to Washington, D.C., where the federal government intended to place him on trial for conspiring to impair the lives of Union prisoners of war.
In July 1865, the trial convened in the Capitol building and lasted two months, dominating the front pages of newspapers across the United States. The court heard the testimony of former inmates, ex-Confederate officers and even nearby residents of Andersonville. Finally, in early November, the commission announced that it had found Wirz guilty of conspiracy as charged, along with 11 of 13 counts of murder. He was sentenced to death.
In a letter to President Andrew Johnson, Wirz asked for clemency, but the letter went unanswered. Wirz was hanged and later buried in the Mount Olivet Cemetery in Washington, D.C. He was survived by his wife and one daughter.
Henry Wirz was the only man tried, convicted and executed for war crimes during the Civil War. His conviction is controversial still today.
Many people today feel that Wirz was unfairly tried and convicted because of the fact that the South had low food rations, which this was out of Wirz's control. In fact, in many instances, the South was unable to feed its own soldiers as the war progressed. Additionally, many historians have reported over the years that Union prison camps were just as harsh as anything experienced in Andersonville, yet no trials addressing the conditions in Federal prison camps were ever held. Wirz's trial and conviction also served to overshadow the many atrocities that were perpetrated at the Union prison camps.