Todd, seeking a rare hat-trick of consecutive victories on the PGA Tour, used another sublime putting display to card eight-under-par 62 on the Seaside course at Sea Island.
It was just about the worse score he could have shot, as he lipped out several putts, including a 30-foot birdie chance at the last that left him laughing when it caught a large part of the cup but refused to drop.
Todd posted an 18-under 194 total with one round left.
Fellow American Webb Simpson (63) and Colombian Sebastian Munoz (66) are equal second on 16-under.
Todd was ranked 525th in the world before winning the Bermuda Open three weeks ago.
He followed up with victory at last week's Mayakoba Classic in Mexico.
A win on Sunday would make him the first player since Tiger Woods in 2006 to win three consecutive PGA Tour events.
Dustin Johnson in 2017 was the last to win three straight starts, though he skipped a tournament during that run.
(Reporting by Andrew Both in Cary, North Carolina; Editing by Ken Ferris)