Brad Faxon and Scott McCarron, who have teamed to win this event twice, fired a 63 of their own to finish alone in second at 14-under-par 130.
The Franklin Templeton Shootout features 12 two-man teams competing in multiple formats over three days at Tiburn Golf Club and Saturday called for Better Ball, with Sunday's play to be contested in scramble fashion.
Perry and Hoch began to pull away from the field with a birdie at the ninth. Hoch continued his fine play with a six-footer for birdie at the 10th before adding a birdie at the 11th to make it three in a row and give his squad a two-shot advantage.
The duo fell off the pace down the stretch but they managed to grab a share of the lead at minus-14 with an eagle at the par-5 17th.
Perry and Hoch added a birdie at the last to secure the outright lead with one round to play.
'You always want to be in the lead,' said Perry, a three-time winner on the PGA Tour this season. 'If we play well, they won't catch us.'
Faxon drained a 12-foot putt for a birdie at the 10th and McCarron followed that up with a birdie at the 11th. At the par-4 13th, McCarron landed his approach inside six feet and rolled in the putt for another birdie.
McCarron sent his second shot from the waste area at the par-5 14th to 12 feet for an eagle to give his team the lead at 12 under par.
Faxon then ran home a 16-foot putt for a birdie at the 16th and the duo added a birdie at the 17th to reach 14 under but in the end it was only good enough for second place alone.
'Playing together helps a lot,' said Faxon, who has won this title twice with McCarron. 'It's nice to have a guy like Scott who can bomb it. We want to have fun.'
Chad Campbell converted a seven-foot putt for an eagle at the par-5 17th help his team move into a tie for third. Campbell, who is teamed with reigning PGA champion Shaun Micheel, posted a 63 to join Mark O'Meara and John Cook at 12-under-par 132.
Jeff Sluman and Hank Kuehne, who held the lead after Round 1, carded a 68 to finish four shots off the pace at 11-under-par 133.
Defending champions Rocco Mediate and Lee Janzen joined Matt Kuchar and Fred Funk in a tie for sixth at 9-under-par 135. Tom Kite and John Huston followed at 8-under-par 136 after a round of 64.
Craig Stadler and Peter Jacobsen finished alone in ninth place at 7-under-par 137. Paul Azinger and Olin Browne were one shot further back at 6-under-par 138.
Tournament host Greg Norman and partner Steve Elkington finished at 3-under-par 141 while the duo of Rich Beem and Mark Calcavecchia held the 12th spot at 2-under-par 142.
Day 2 Four-ball Results:
1. Kenny Perry/Scott Hoch -15 (63)
2. Brad Faxon/Scott McCarron -14 (63)
T3. Shaun Micheel/Chad Campbell -12 (63)
T3. Mark O'Meara/John Cook -12 (64)
5. Jeff Sluman/Hank Kuehne -11 (68)
T6. Matt Kuchar/Fred Funk -9 (68)
T6. Rocco Mediate/ Lee Janzen -9 (66)
8. Tom Kite/John Huston -8 (64)
9. Craig Stadler/Peter Jacobsen -7 (68)
10. Paul Azinger/Olin Browne -6 (70)
11. Greg Norman/Steve Elkington -3 (69)
12. Rich Beem/Mark Calcavecchia -2 (70)