He was admitted to the South Carolina bar in 1839, practiced law with his father, and was a very respected member of Columbia society.

In 1858, he issued the secessionists' manifesto in a pamphlet entitled, "An Appeal to the State Rights Party of South Carolina."

In it, Gregg argued that Carolinians had looked unfavorably upon and rejected incorporation into the Democratic Party since the tariff controversy.

Gregg gained prominence at the Second Battle of Bull Run when his men repulsed six Union assaults, and he served in Robert E. Lee's Maryland Campaign.

However, doctors pronounced the wound mortal, and Gregg died on December 15, saying on his deathbed "I yield my life cheerfully, fighting for the independence of South Carolina.