Fowler and DeChambeau both carded five-under 66s at TPC Scottsdale for 10-under-par 132 totals, one stroke clear of compatriots Daniel Berger and Chez Reavie.
Scott Stallings (65), Chesson Hadley (68) and Chris Kirk (68) were 8 under, and Phil Mickelson (65) and fellow former Arizona State player Jon Rahm (68) topped the group at 7 under.
Two-time defending champion Hideki Matsuyama withdrew on Friday from the Waste Management Phoenix Open due to an injury at the base of his left thumb.
The Japanense, ranked fifth in the world, was playing with Webb Simpson and Rickie Fowler - having defeated both in play-offs to win the title in 2016 and 2017.
Matsuyama made a decision to withdraw prior to his second-round tee-time despite being treated for the pain, which started during Thursday's opening round.
He got back on track with bridies at 13 and 15, before a bogey at 17, where a "funky little chip" led to a disappointing dropped shot.
"We're in a good spot going into the weekend", he added. This is a place we know we can continue to play well.
"We'll piece together the nines at some point".
If you've never been to the Phoenix Open, let's just say it's unlike any other PGA Tour event you'll ever experience. Things also carry over into the drivable par-4 17th.
World number three Jordan Spieth missed the cut by one shot, the American finishing on even-par 142 to suffer his first weekend off since last May.