DALLAS, May 18, 2014 (AFP) - Oosthuizen, the 2010 British Open champion, and Todd each closed with a birdie to finish 54 holes on 10-under 200.
"Every opportunity I had for birdie, I actually made," Oosthuizen said.
One stroke off the pace were Canadian left-hander Mike Weir, the 2003 Masters champion, and Americans James Hahn and Gary Woodland.
Irishman Padraig Harrington, Canada's Graham DeLaet, Australian Marc Leishman and American Morgan Hoffmann were on 202, Hoffmann having double-bogeyed the 18th to fall from a share of the lead.
Oosthuizen opened with a bogey and took another at the fourth but answered with three birdies in a row starting at the par-3 fifth, with his eight-foot birdie putt there the longest such effort of the run.
Oosthuizen began the back nine with a birdie, then ran off three more in a row culminating at the par-5 16th after his eagle effort stopped inches shy of the hole.
The South African then closed with a four-foot birdie putt.
Oosthuizen, who withdrew from the event a year ago because of a neck injury, fired the lowest round of the day and his lowest US PGA round since late in 2012.
Injuries have nagged Oosthuizen since, with only one round in the 60s in US events before this week.
"The last year and a half was really frustrating for me," Oosthuizen said
Todd, who led a PGA round for the first time after Friday, has never cracked the top-five at a PGA event but could collect a record payday by claiming the $1.242 million top prize Sunday.
Todd fired a 68, sandwiching birdies at the third and fifth around his lone bogey of the day. He made 12 pars in a row until his closing birdie from four feet to reach the final pairing.
Hoffmann reached the final hole sharing the lead but took a drop after a poor tee shot, found a greenside bunker and could not escape the sand pit on his fourth shot. He blasted out and made a six-footer for double bogey.
Weir, who turned 44 last Monday, seeks his first top-10 showing since 2010 in his 401st career start. He has not won a PGA title since the 2007 Fry's Open, but would become the oldest winner on tour this year.
Dallas 17-year-old amateur Scottie Scheffler aced the 218-yard second hole with a 5-iron.
Woodland sank another improbable shot, holing an 87-yard putt at the par-4 12th.
Leading third-round scores on Saturday from the $6.9 million US PGA Tour Byron Nelson Championship (USA unless noted, par-70):
200 - Louis Oosthuizen (RSA) 68-68-64, Brendon Todd 68-64-68
201 - James Hahn 71-65-65, Gary Woodland 68-67-66, Mike Weir (CAN) 68-66-67
202 - Padraig Harrington (IRL) 68-68-66, Marc Leishman (AUS) 66-68-68, Graham DeLaet (CAN) 68-66-68, Morgan Hoffmann 68-66-68
203 - Greg Chalmers (AUS) 71-67-65, Boo Weekley 67-68-68, Charles Howell 68-66-69
204 - John Huh 67-71-66, Matt Kuchar 69-67-68
205 - Aaron Baddeley (AUS) 68-70-67, Vijay Singh (FIJ) 69-68-68, Martin Kaymer (GER) 67-67-71
206 - Dustin Johnson 69-69-68, Scott Gardiner (AUS) 70-69-67, Lee Williams 67-71-68, Keegan Bradley 70-68-68, Robert Garrigus 74-64-78, Andres Romero (ARG) 71-66-69, Charlie Wi (KOR) 73-67-66, Retief Goosen (RSA) 70-65-71, Ryan Palmer 67-68-71