Mike McCullough and Des Smyth each shot 67s, while Jay Sigel and Allen Doyle each carded 68s to move into a tie for second place at 4-under-par 140.
Fernandez jumped out of the gates quickly at The National Golf Club of Kansas City. He two-putted for birdie at the par-5 second and followed that with another birdie from six feet out at the par-3 fourth.
The Argentinean then rolled in a 35-footer for an eagle putt at the par-5 fifth. He managed three straight pars before bogeying the ninth to make the turn at minus-4.
On the back side, Fernandez drained a five-footer for birdie at the par-4 12th, but dropped a shot at the next hole when he three-putted.
He secured first place with back-to-back birdies from the par-5 15th. He got up-and-down for birdie at the 15th, then drained a 15-footer for birdie on 16.
'I took advantage of most of my opportunities today,' said Fernandez. 'I won't play any different (tomorrow) than I've been playing. A lot of guys will try to catch me (Sunday).'
Fernandez, who won the ACE Group Classic earlier this year, will look to pick up his fifth Champions Tour title on Sunday.
'The win in Naples was big. I had put a lot of pressure on myself to do well before that,' Fernandez said. 'I was putting a little better then, but I might be striking the ball better now.'
McCullough also started quickly as he rolled in a 15-footer for eagle at the second. However he was unable to maintain that momentum as he bogeyed two straight holes from the par-3 sixth.
He made up for those bogeys with back-to-back birdies, both from within 10 feet, from the eighth to head to the back side at minus-1.
Around the turn, McCullough notched back-to-back birdies from the 11th and again from the 14th to briefly climb to minus-5. He faltered with a bogey at the 17th to drop him into a share of second.
'That was a big swing the last few holes there,' McCullough said. 'Tomorrow we'll find out whose nerves are strong.'
Smyth stumbled out of the gate with a bogey at the par-4 first. He quickly atoned for that mistake as he birdied the next two holes. Smyth then moved to 2-under with an eagle at the par-5 fifth.
The Irishman ran off five straight pars before dropping a shot with a bogey at the 11th. He was able to join the group at minus-4 as he birdied the 13th, before back-to-back birdies from the 15th.
'I got off to a bad start, but the eagle at No. 5 changed the complex of my game,' Smyth said. 'Lots of guys have a chance to win. I've been struggling with my form, so that will be tested on Sunday.'
James Mason and Butch Sheehan are tied for sixth place at 3-under-par 141. Hale Irwin, Tom Jenkins, Pat McDonald and Dave Stockton share eighth place one-stoke further back. McDonald's 7-under 65 was the low round of the tournament and helped him jump up 40 spots.
Overnight leader Jose Maria Canizares struggled to a 3-over 75. He stands at even-par 144 and shares 17th place with four other players.