Moises Henriques (53no) produced a captain's knock to secure his wounded outfit's win at the SCG on Monday night, their first step towards avenging a heartbreaking loss to the Brisbane Heat in last summer's final.
Chasing the Renegades' 7-169, Sixers allrounder Ben Dwarshuis (14no) hit the winning runs down the ground for four in the 19th over, as his side finished at 5-172 with nine balls to spare.
"It got a little nervy there for a bit," Henriques said.
"(But) we still had batting in the sheds. I thought we bowled really well, it was a pretty good batting wicket, they had to take a lot of risk to hit their boundaries and they had a bit of luck to get to 169.
"I thought we brought it back really well."
After the Sixers sent the visitors in, Hughes aggravated an elbow injury diving in an unsuccessful attempt to catch Tim Seifert (55) - the Renegades' top-scorer.
It was the latest in a series of setbacks for Hughes, who had finally been given the chance to cement his spot after two summers in and out of the team.
"It's very concerning about 'Hughey'," Henriques said
"I'm not sure what the diagnosis is. I'm hopeful it's good but he wasn't even able to hold the bat tonight."
Hughes's injury forced the Sixers to pump Jack Edwards (37) up to first drop where he forged the innings' best partnership with Englishman James Vince (40) with a 62-run stand for the second wicket.
Tim Seifert was the backbone of the Renegades' innings, with 55 off 42 balls. (Mick Tsikas/AAP PHOTOS)
Renegades skipper Will Sutherland (2-20) provided strong resistance, bowling Vince then having Joel Davies caught behind.
Just as Henriques and allrounder Kerr appeared to be hitting their stride, the latter called for medical attention.
He retired hurt but Henriques said he had only been cramping so will play in Saturday's match against rivals the Sydney Thunder.
"We were hoping that it would go away and he'd be all right," Henriques said.
"Unfortunately he sort of felt like he couldn't put any weight on it."
The Renegades will have rued a missed opportunity for a run out when the game was on tilt.Â
Sydney Sixers were in the pink as they edged a competitive first BBL outing of the new campaign. (Mick Tsikas/AAP PHOTOS)
Although Henriques had slipped over running between wickets, Tom Rogers' throw from mid-wicket could not connect with the stumps.
A dismissal would have left the Sixers teetering at 6-126 requiring 44 in five overs with Hughes in the sheds unlikely to come in to bat.
Instead, Henriques clubbed Rogers for four from the next ball in a sign of things to come.
When he smacked Australian white-ball superstar Adam Zampa for two sixes in the 18th over, the Sixers could smell victory to open their campaign.
Henriques has now scored 17 half-centuries for the Sixers, moving past Josh Philippe as the club's most successful player for that metric.
Earlier, New Zealand white-ball regular Seifert enjoyed a BBL debut to remember, showcasing his reverse sweep, and at one stage lifting Sean Abbott over deep midwicket for six.
But after he lost control attempting to belt Dwarshuis (2-42) into the stands and gave an edge to wicketkeeper Josh Philippe, the Renegades' innings never reignited.
Sean Abbott (2-34) was also important with the ball for Sydney, enticing the dangerous Jake Fraser-McGurk (21) into skying to Dwarshuis from his first delivery.
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