Born in 1770 in Rowan County, North Carolina, Waddel graduated in 1791 from Hampden - Sydney College with a Bachelor of Arts (B.A.) and was licensed to preach by the Presbytery of Hanover.

Waddel (pronounced Waddle) began his ministry in the low country of South Carolina, but coming to view Charleston, South Carolina sophistication as sinful, departed for the backwoods 'upcountry'. In 1794, he founded his first 'log cabin academy' at Carmel near Appling in Columbia County, Georgia. In 1801, Waddel moved to Vienna and then Willington, South Carolina, where he founded the famous Willington Academy in 1804. These prep schools trained the future elite of Georgia and South Carolina with a strict classical education, in an environment shrewdly calculated by Waddel to foster self reliance and self motivation. Graduates generally entered university at the Junior year. The Debating Society in Augustus Baldwin Longstreet's Georgia Scenes takes place at Willington and, as written by Longstreet himself, "is as literally true as the frailty of memory would allow it to be."

In 1819, Waddel further enlarged his fame with Memoirs of the Life of Miss Caroline Elizabeth Smelt. Difficult reading today for its overwrought and pious sentimentality, Memoirs was a smash bestseller reprinted in the U.S. and Great Britain.

Considered the foremost educator in the South, Waddel "received an urgent and persistent invitation" to revitalize the University of Georgia (UGA) in Athens. He became the fifth president and served from 1819 until his resignation in August 1829. Waddel found the school "nearly extinct, consisting of only seven students with three professors". With great industry he scoured the state and soon built enrollment to one hundred students. He acquired money for the library, garnered state funding, and raised three new buildings: Philosophical Hall (1821), New College (1823) and Demosthenian Hall (1824). As said by Longstreet, "The effect of his coming to this Institution was magical. It rose instantly to a rank which it had never held before, and which, I am happy to add, it has maintained ever since."

Waddel was said to possess only an ordinary intellect but combined with an iron will. This 'Cromwell of the Classroom' produced a generation of Southern leaders including William H. Crawford, Madison’s Secretary of the Treasury and 1824 US Presidential candidate; Hugh S. Legaré, editor of the Southern Review; Governor and U.S. Senator George McDuffie of South Carolina; Judge James L. Petigru, the Unionist who famously stated that South Carolina was too small to be a nation and too large for an insane asylum; Governor George Rockingham Gilmer of Georgia; Judge Augustus Baldwin Longstreet, author of Georgia Scenes and president of two universities, and John C. Calhoun. Andrew Jackson is said to have (perhaps mistakenly) claimed Waddel's influence.

According to Dr James McLeod's book 'The Great Doctor Waddell' the list of students from all of Waddell's schools includes: two Vice-Presidents, three Secretaries of State, three Secretaries of War, one Assistant Secretary of War, one US Attorney general, Ministers to France, Spain and Russia, one US Supreme Court Justice, eleven governors, seven US Senators, thirty two members of the US House of Representatives, twenty two judges, eight college presidents, seventeen editors of newspapers or authors, five members of the Confederate Congress, two bishops, three Brigadier generals, and one authentic Christian martyr.

Waddel died on July 21, 1840, in Athens, Georgia.