Langer posted a 12-under 130 halfway total, while American Russ Cochran also carded 65 to move into second place on eight under.
American Steve Pate fired a course-record 63 to vault into a tie for third, six shots behind Langer.
The German has led or co-led a senior major after 36 holes on seven occasions, so he is no stranger to playing from the front.
He could go wire-to-wire in a senior major for the second straight year, after last year's Senior British Open, which he won by 13 strokes.
The 57-year-old won two majors on the regular tour, 1985 and 1993 Masters, and has four senior major victories.
He has dominated the senior circuit since turning 50, winning the money title six of the past seven years.
(Reporting by Andrew Both in Cary, North Carolina; Editing by Greg Stutchbury)
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