Earlier, three wickets in over and career-best figures by Hurricanes fast bowler Hayley Silver-Holmes (3-18 off three) rocked her former side in a deserved player of the match display.
The opening stand of 95 between Lee (55 off 33 deliveries) and Wyatt-Hodge (45 off 26) rollicked along at more than 10 runs per over and allowed the Hurricanes to coast to victory at North Sydney Oval on Thursday.
The Sixers had made 9-152 but the Hurricanes were never troubled in the chase and won with 19 balls remaining to stay undefeated.
Lee slammed the bowlers to all parts of the ground.
The experienced masterblaster showcased all her skills and combined power and touch in equal measure to notch her 12th WBBL half-century to go with her five hundreds.
Wyatt-Hodge, fresh from a brilliant 90 in her last match, dominated on the offside where she placed the ball to perfection.
The England star also lofted two sixes over the leg side that went through the hands of Sixers fielders.
The pair's opening stand was the highest in Hurricanes history.
After being sent in, the Sixers were 2-92 after 12 overs and appeared set for a 170-plus total before Silver-Holmes took three wickets in one over.
She had the dangerous Ash Gardner (nine) out pulling a delivery that hurried on.
Next ball Silver-Holmes knocked over Amelia Kerr with an off-cutter.
Another off-cutter to Alyssa Healy (37 off 26) went through the gate to cap a tremendous over.
The 22-year-old didn't play last year's WBBL series due to an elbow injury that required surgery.
"I've had a really bad few years with injuries but I think the big thing for me was getting as fit as I could," Silver-Holmes said.
"That makes it that much easier to do what I do."
She was humble about her decisive over that turned the match.
"When things are happening, they are happening. That's T20 cricket," Silver-Holmes said.
"It was all a bit of a blur but I'm super pumped to get the win."
Healy, playing her first WBBL match of the season after recovering from a hand injury, used the pace off the pitch to perfection in her cameo and in combination with Ellyse Perry (33 off 29) had looked in control.
Perry smoked six boundaries, with her shots through the cover region sublime, before Heather Graham cleaned up her stumps.
Graham, fifth on the all-time WBBL wicket list, bowled with guile. Her seamers moved both ways and challenged the strong Sixers top order.
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