Thomas Fortune Ryan was born near Lovingston, a small Nelson County community south of Charlottesville, Virginia. Despite certain myths regarding his background, Ryan was neither orphaned nor penniless as a youth and he traced his ancestry to Protestant Anglo-Irish settlers in the 17th century.

At age 17, Ryan perceived a lack of economic opportunity in post-war Virginia and so moved across the border to the city of Baltimore. En route to Maryland, Ryan converted to Catholicism after long discussions with a fellow passenger on the train.

In Baltimore, John S. Barry, a prosperous dry goods merchant, hired him. By 1872, Barry helped Ryan secure a brokerage assistant position on Wall Street where he would be tutored by William Collins Whitney.

The Thompson Submachine Gun was developed by General John T. Thompson who originally envisioned an auto rifle (semi-automatic rifle) to replace the bolt-action service rifles then in use. While searching for a way to allow such a weapon to operate safely without the complexity of a recoil or gas operated mechanism, Thompson came across a patent issued to John Bell Blish in 1915 based on adhesion of inclined metal surfaces under pressure. Thompson found a financial backer, Thomas Fortune Ryan, and started the Auto-Ordnance Company in 1916 for the purpose of developing his auto rifle. Ryan contributed all the research and development funds to get the company started.

Some of the first batches of Thompsons were bought in America by agents of the Irish Republic, notably Harry Boland. The first test of a Thompson in Ireland was performed by West Cork Brigade commander Tom Barry in presence of IRA leader Michael Collins. A total of 653 were purchased, but 495 were seized by US customs authorities in New York in June 1921. The remainder made their way to the Irish Republican Army by way of Liverpool and were used in the last months of the Irish War of Independence (1919–21). After a truce with the British in July 1921, the IRA imported more Thompsons and they were used in the subsequent Irish Civil War (1922–23). They were not found to be very effective in Ireland however. In only 32% of actions where it was used did the Thompson cause serious casualties (death or serious injury) to those attacked.

And so it was that an Irishman was the main financial backer of the Auto-Ordnance Company at formation in 1916. He had a controlling interest with 18,000 out of 40,000 issued shares. He had made his money from tobacco. He was a member of Clan na Gael and a friend of John Devoy as well as a contributor to the American Committee for Relief in Ireland.

On 23 November 1928, Thomas Fortune Ryan died, the South’s wealthiest native son and the nation’s 10th wealthiest man. He was buried at Oak Ridge, where his second wife, Mary, was also interred, leaving a fortune of more than $200 million.