CHARLOTTE, 16 May 2015 (AFP0 - Simpson's second straight 67 gave him a 10-under total of 134, tied with first-round leader Streb, who carded a 69.
They were two strokes in front of Americans Martin Flores and Patrick Rodgers, Flores posting a 67 and Rodgers a 68 for eight-under 136.
McIlroy, meanwhile, made the most of his good breaks, firing five birdies without a bogey in a 67 that left him tied for fifth on 137 alongside five-time major champion Phil Mickelson (66) and Will MacKenzie (68).
McIlroy opened his round with an impressive birdie at the par-five 10th, where he rolled in a 30-foot birdie putt from off the green.
"It's always nice to start the day with a putt like that," said McIlroy, who missed five fairways but found the green at each of those holes.
"Thankfully, it went my way today," said McIlroy, who captured his first US PGA Tour title at Quail Hollow in 2010.
McIlroy thought his score could have been even better, but he wasn't complaining.
"I think I've gotten a lot better at staying patient," he said. "The way I hit it today, I felt like I could have shot 63 or 64, but (I'm) realizing 67 is still a good score and puts me in a great position going into the weekend."
McIlroy's easy confidence could be bad news for the players in front of him.
Simpson, a local favorite who is enjoying some extra time with family that comes from playing at home, grabbed his share of the lead with the help of two chip-in birdies, at the par-four ninth and at the tough par-three 17th.
"They were different," Simpson said of the birdie chips. "At nine I had a kind of bad lie in the rough and I chunked it out of there and it released for me.
"At 17 I had a tight lie. It's a tough shot but it came out just right -- that was a fun atmosphere at 17."
Streb, who is seeking a second title of the season after winning the McGladrey Classic in October, made his first bogey of the week at the par-four 16th, but clung to a share of the lead with two pars to finish.
"It's been going good," Streb said. "My misses haven't got me in too much trouble with the exception of 16.
"I'm just kind of hanging around, making some putts. Hopefully I'll hit it nice and solid over the weekend and keep the putter going."
Leading second-round scores on Friday in the US PGA Tour's $7.1 million Wells Fargo Championship (USA unless noted, par-72)
134 - Webb Simpson 67-67, Robert Streb 65-69
136 - Martin Flores 69-67, Patrick Rodgers 68-68
137 - Rory McIlroy (NIR) 70-67, Will MacKenzie 69-68, Phil Mickelson 71-66
138 - Russell Knox (SCO) 69-69, Geoff Ogilvy (AUS) 69-69, Michael Thompson 67-71, George McNeill 69-69, Brendan Steele 69-69
139 - Kevin Chappell 66-73, Scott Gutschewski 69-70, Matt Jones (AUS) 69-70, Scott Brown 71-68, Shawn Stefani 69-70, Daniel Berger 71-68
140 - Ricky Barnes 67-73, Steve Wheatcroft 74-66, Patrick Reed 66-74, Chad Campbell 71-69, Jason Bohn 72-68, Tony Finau 73-67, Carl Pettersson (SWE) 68-72, Jim Herman 71-69, Kevin Streelman 69-71, K.J. Choi (KOR) 68-72, Hideki Matsuyama (JPN) 69-71, Danny Lee (NZL) 71-69, Brian Stuard 70-70