The Sixers have now won five of their seven BBL matches this season to sit on 10 points and only be net run rate behind the second-placed Perth Scorchers with a game to play.
The Sixers now finish their BBL campaign against the bottom-placed cross-town rivals the Sydney Thunder at ANZ Stadium next Saturday night while the Scorchers have a tough ask of needing to be the first team to beat the Melbourne Stars to guarantee a home semi-final.
The equation is simple and if the Scorchers win, they will host a semi-final at the WACA Ground while if Perth loses and the Sixers beat the Thunder, then the Sydney-siders will host the semi-final at the SCG.
Either way, it now appears locked in that the Scorchers and Sixers will meet in a BBL semi-final with just the venue to be confirmed while the Stars are also guaranteed of finishing top and to host the other semi with the Brisbane Heat, Hobart Hurricanes and Adelaide Strikers still in the running for that fourth spot.
After the loss at home on Saturday night, the Renegades are now out of the running for a final spot as are the Thunder.
While the final score of the Sixers beating the Renegades by two runs makes it appear it was a tight affair, the Sixers were rather convincing winners with only a six off the last ball from Ben Rohrer bringing the home team to within the two runs.
The Sixers batted first and with Moises Henriques (55), Marcus North (30 not out) and Steve Smith (25) playing well, managed to scrape to what appeared at least a competitive score of 6-151 from the 20 overs.
While the Renegades made a decent start, they lost regular wickets and kept slipping further and further behind the required run-rate and ended up finishing on 5-149 from their 20 overs to fall short of the win.
The Renegades were without Australian pair Aaron Finch and James Pattinson with Rohrer taking over from Finch as captain.
He won the toss and elected to field first and it paid off immediately when just seven balls in Nic Maddinson was out for three when stumped by Peter Nevill off the spin bowling of Aaron O'Brien.
The Sixers then steadied through a 46-run second wicket partnership between Michael Lumb and Henriques before Lumb fell in the sixth over for 18 with the score 2-52.
Smith and Henriques then came together and put on 46 for the third wicket but Smith never really got going hitting the boundary just the once, admittedly a massive second level six off Matt Gale, before he was out caught and bowled O'Brien for 25 from 22 balls.
Henriques appeared to hold the key to the Sixers posting a good total but he was out in the 15th over for a well made 55 from 39 balls with seven fours and a six when stumped by Nevill off Muttiah Muralitharan.
At that stage, the Sixers' innings could go either way at 4-109 with 34 balls remaining.
Jordan Silk struggled to 10 from 15 balls before being bowled by Dwayne Bravo and then David Smith was out first ball LBW to Nathan Rimmington, but Marcus North took care of things for the Sixers.
He finished 30 not out from 21 balls with two fours and a six to help the Sixers make 6-151.
Rimmington finished with the figures of 2-35 from four overs for the Renegades with O'Brien taking 2-41, Bravo 1-23, Muralitharan 1-23 and Gale 0-27.
The Renegades knew they needed to chase down the total to keep their finals hopes alive and they got off to a solid start with an opening partnership of 36 between Dan Harris and Michael Hill.
Their partnership ended when Harris was run out for 20 but Hill continued to look solid making 35 with two sixes before he was caught at long-on by Maddinson from the bowling of Henriques.
Alex Doolan then struggled to 19 before being run out and Bravo looked capable of becoming the match-winner for the Renegades hitting two sixes on his way to 38, but that was as far as he went before falling to a good catch by Nathan Lyon off Josh Hazlewood.
Rohrer did his best to still win the game for the Renegades and finished 28 not out from 20 balls, but ultimately he and his team fell two runs short.
Hazlewood finished with 1-22 from four overs with the ball for the Sixers with Henriques taking 1-29, Steve O'Keefe 0-22, Lyon 0-39 and Brett Lee 0-34.