Yang, who won his first major title after overhauling Tiger Woods at the PGA Championship in August, fired a sparkling seven-under-par 65 on another benign day of sunshine at Sherwood Country Club.
Helped by a chip-in from greenside rough to birdie the par-three 15th, the Korean posted a nine-under total of 135 in the limited field event usually hosted by world number one Woods.
Woods pulled out of the event on Monday, citing injuries from a car crash outside his Florida home last week as speculation began to escalate over his private life.
On Wednesday, he apologised for “transgressions” in a statement that apparently addressed allegations he had extra-marital relationships. Yang covered the back nine in three-under 33 to end the day two ahead of American Kenny Perry (65), Irishman Padraig Harrington (68) and Britain’s Ian Poulter (69).
Former Masters champion Zach Johnson, co-leader overnight with Poulter, was among a group of three players at six under after carding a 70.
Yang, who became Asia’s first male major champion with his spectacular breakthrough at Hazeltine National, took control of the tournament despite an erratic display on the greens.
“My putter didn’t really work for me,” he told reporters through an interpreter. “I think I missed three or four short putts today.”
He was determined to keep playing on in the tournament however, even though his health has steadily deteriorated since Monday.
“I’m coming down with flu or a fever,” Yang said. “I had a pounding headache when I started today and I chucked in some medicine but it wore off on the back nine.”
Yang said he would not contemplate pulling out if his condition worsened.
“No,” he replied after a brief pause.
“If I do collapse, I will collapse on the golf course and I will withdraw on the golf course.”