Chasing 151 after the Strikers made 4/150 at Metricon Stadium, the reigning BBL champions reached their target with 12 balls to spare.
The Sixers made a blistering start to their chase with Jack Edwards (14 off 10) and Josh Philippe (41 off 24) smashing 47 in the four-over powerplay.
The end of the fielding restrictions brought Afghan spinner Rashid Khan into the attack he removed both Sydney openers to have them 2/58. The leg-spinner would strike once more to dismiss Sixers' captain Daniel Hughes (12) and ended the night as the pick of the Strikers' bowlers with 3/18 from his four overs.
The Sixers' confident run chase came after a half-century by Jonathan Wells lifted an altered Strikers' batting line-up.
Wells scored 66 off 56 deliveries before being caught of the final ball of the Strikers' innings, which needed a late flurry after a horrid start.
Following their New Year's Eve loss to the Perth Scorchers, the Strikers tweaked their batting order with ex-Test player Matt Renshaw moving to opener and Jake Weatherald dropping down to No.5.
That plan didn't pay off however with Renshaw and opening partner Phil Salt (1) falling inside the first two overs to leave the Strikers 2/7, before late burst which yielded 43 runs off the last three overs between Wells and Weatherald (34 not out), lifting the Strikers to 150.
Adelaide will look to get back to winning ways on Tuesday when they host the last-placed Melbourne Renegades at Adelaide Oval.