Four cars that started the 161 laps inside the top 10 have struck trouble, including Jamie Whincup/Paul Dumbrell's Red Bull Commodore that shed a wheel.
The 2012 winners are a lap down in 23rd, while team-mates Shane van Gisbergen/Earl Bamber had a slow fourth pitstop and are 16th.
An intra-Tickford clash accounted for Cameron Waters/David Russell and James Courtney/Jack Perkins are out with an engine failure.
In cool but sunny conditions, Reynolds led the field away off the line, as Anton De Pasquale and van Gisbergen jumped Whincup through the opening stages to move into second and third.
Reynolds edged away, his margin helped by De Pasquale running wide at The Chase on lap three and losing second, then being passed by Whincup one lap later.
His advantage over van Gisbergen had grown to nearly five seconds before the first round of pitstops - when co-drivers replaced full-timers in most cars.
Youlden emerged with a trimmed lead over Bamber and Dumbrell in the Red Bull Holdens, but locked up and ran slightly wide at Turn 1 on lap 28.
That put Bamber and Dumbrell right on his tail, the latter pair trading positions into Griffin's Bend.
Dumbrell stuck with Youlden and the Safety Car was then called on lap 34, when the #25 WAU Commodore suffered an engine failure on Mountain Straight with Perkins behind the wheel.
Everybody pitted, with Bamber having to double-stack behind Dumbrell and losing places to Alex Premat, Steven Richards and Chaz Mostert, whose co-driver James Moffat started.
From second place on lap 40, Dumbrell's Commodore shed its right-front wheel coming down the front straight, resulting in a slow crawl back to pitlane.
The #1 Holden is currently circulating in 23rd place with Dumbrell back behind the wheel, one lap down, and battling minor suspension damage sustained in the lap spent on three wheels.
After Dumbrell's demise, Premat passed Youlden for the lead on lap 45, and got away to the tune of nearly two seconds by lap 50, while Youlden by then had Mostert, Steven Richards and Bamber for company.
The next round of pitstops brought trouble for the #17 Shell Ford and the #888 Autobarn Holden in the form of a slower stop and off at pit entry for Richards respectively.
Coulthard - slightly off sequence - inherited the lead from Reynolds and van Gisbergen, with McLaughlin and Lowndes back in seventh and 13th on lap 60.
The #12 Shell Ford pitted on lap 69 with Coulthard handing over to D'Alberto and Reynolds taking the lead at the same time.
As light rain fell briefly at the top of the Mountain, still on slicks, Reynolds pulled away to lead van Gisbergen by nearly 10 seconds.
The race was neutralised by a second Safety Car period on lap 76 for debris on the circuit, which timed in nicely with a fourth round of pitstops for the full field.
This was the #97 Red Bull Holden's turn to have a slow brake change, falling to 16th in the order with Bamber behind the wheel.
When racing resumed on lap 79, Youlden led D'Alberto, Luff, Moffat and Richards, after Lowndes picked his way back up the order.
Garry Rogers Motorsport pair Richard Muscat and Chris Pither were sixth and seventh, the latter entry having started 10th but run fifth early with Garth Tander behind the wheel.
Premat was eighth ahead of Will Brown, Macauley Jones and Garry Jacobson in the lead Nissan.
Joined by Brown, De Pasquale's early flourish became a memory when troubles with the passenger door on the #99 Commodore would not stay shut.
An extra pitstop to tape it up with Will Brown behind the wheel dropped it outside of the top 20. The pair have clawed their way back into the top 10.
Tickford Racing's lead starter was Waters in sixth, but the Monster Falcon was also the first to strike serious trouble in the race.
Waters had just handed over to co-driver Russell when it tangled with the sister Ford driven by Mostert at Forrest's Elbow on lap 22.
Mostert clipped the inside wall, which fired it into the Monster Ford and Russell into the outside wall, doing steering damage, leaving it 13 laps down after repairs.