Reed, who turned 23 last week, shot a 6-under-par 64 at the Sedgefield Country Club for a two-day total of 129.
He missed four cuts in a row earlier this year, but has finished among the Top 10 in three of his last six starts and will easily make the field for the FedEx Cup playoffs that begin next week.
One shot behind was John Huh, also 23, the PGA Tour's 2012 rookie of the year who turned in a 62 Friday. And two shots off the lead was Jordan Spieth, who became the youngest winner on the tour in 84 years when he captured the John Deere Classic last month at age 19.
Spieth, having turned 20 since that victory, birdied four of his last six holes to shoot a 66 for his 131 total.
PGA Championship winner Jason Dufner is not playing this week, nor are any of the other major winners from the 2013 season.
This is the last of the tour's regular events for the season, making it a vital week for those on the edge of earning enough points to get into the playoffs or enough money to keep their place on the exempt list for next year. The Top 125 players on the points list will tee off in the playoffs and the leading 125 money winners earn a spot on the 2014 circuit.