The home side looked like they would continue their unbeaten start to join Hobart Hurricanes at the top of the BBL ladder after the Sixers posted a seemingly paltry 7-132 on Saturday after being sent in.
Their top order again failed to fire, making just 25 runs in the batting power play while losing three wickets to pile the pressure on to their middle order.
But the Renegades, who made the semi-finals last season, failed to handle the Sixers' spin brigade led by debutant off-spinner Ben Manenti and only managed 9-99 in reply.
Manenti has sporting pedigree, albeit in rugby rather than cricket with his father John the coach of the Australian women's sevens rugby team.
The 21-year-old finished with figures of 2-13 from his four overs after only finding out just an hour before the match he was going to be playing.
"It was awesome but it hasn't really sunk in yet," Manenti said.
"I knew we were going with a spinner but I didn't know it was me but the late notice probably wasn't a bad thing as it didn't give me much time to think about it."
Manenti took the wicket of another debutant, teenager Mackenzie Harvey, who also has family sports ties.
The nephew of former Australian allrounder Ian Harvey, Mackenzie Harvey top scored with 30 from 25 deliveries, including a six and four fours.
As well as Manenti, fellow spinner Steve O'Keefe also troubled the Renegades with figures of 2-19.
Their pace attack also deserved some credit with Tom Curran taking three wickets while Sean Abbott collected two scalps.
The Renegades made a reasonable start when 2-38 from six overs but their innings crumbled when they lost three wickets for two runs in the space of nine balls with O'Keefe and Manenti doing the damage.
Skipper Tom Cooper said he thought his team had done enough after limiting the Sixers batting line-up.
"I thought we bowled and fielded pretty good and to keep them to 132, but then we just got completely outplayed with the bat so we will have to have a look at that," he said.
For the Sixers Jordan Silk top scored with 30 from 33 balls before being caught and bowled by Kane Richardson, who took 3-22 from four overs to lead the Renegades attack.