The halfway co-leader mixed six birdies with two bogeys on day three to jump to 16-under-par and establish a one-stroke lead over defending champion Li Haotong with 18 holes remaining.
Li closed his third-round 67 with back-to-back birdies to sit alone in second place, two shots ahead of Ernie Els – a three-time winner of this event – and Matt Wallace on 13 under.
Lucas Herbert, who had led alongside DeChambeau after 36 holes, Challenge Tour graduate Kalle Samooja, 2011 winner Alvaro Quiros and Thorbjørn Olesen were then in a tie for fifth on 12 under.
DeChambeau slipped down the leaderboard after opening his third round with five straight pars, while those around him made birdies.
The World Number Five picked up his first shot of the day at the sixth when his approach hit the flag before landing four feet from the cup, but he carded back-to-back bogeys at the seventh and eighth to fall even further off the pace.
He bounced back with birdies at the ninth and tenth before holing his ten-foot birdie putt at the 13th to grab a share of the lead.
The 25-year-old rolled in his birdie putt from six feet on the 15th green before repeating the trick from around four feet at the 17th to get to 16 under.
After his third round, DeChambeau said: “I can’t express to you how awesome it would be to win on the European Tour.
“I’m still in the lead, still got the job done. I made it happen when necessary and hopefully I can have one more of those days and maybe even a better-ball striking day.”
Li, who is looking to become the first player since Stephen Gallacher to successfully defend this title, made birdies at the second, fourth, sixth and eighth to surge into contention.
He closed his front nine with a bogey but got the shot back when he holed his three-foot birdie putt at the next.
After a series of good pars, Li dropped another shot at the 16th but finished with two birdies from around five feet to get within one shot of DeChambeau.
“It was pretty decent (today). Actually the long game has been way better than the last couple of days. Yeah, it’s just a solid day today.”