Chasing the Lions' 121 all out, Sydney raced to 124 without loss with Michael Lumb smashing his way to a thrilling 82 not out off just 42 balls with eight fours and five sixes.
Sydney, who went through the tournament unbeaten, received $2.5 million (£1.55m) for winning the world club event while the Lions claimed $1.3 million as runners-up.
Earlier, the Johannesburg-based Lions were sent in to bat in front of a sell-out crowd and lost their last wicket off the last ball of their allotted 20 overs, with Jean Symes' 51 off 46 balls top scoring.
New Zealand off-spinner Nathan McCullum, who opened the bowling for the Sixers, claimed 3-24 while paceman Josh Hazlewood nabbed 3-22.
Englishman Lumb, who was born in South Africa, and fellow opener Brad Haddin (38 not out) made light work of chasing down the Lions' total as they scored the winning runs with 45 balls remaining.
The pair were let off during their respective knocks with both dropped.
The Lions' fate was cast in the first innings after they crashed to 9 for four with left-arm spinner Steve O'Keefe effective with the new ball claiming one for 11 off four overs.
Only a career-best knock from Symes saved the Lions from complete humiliation and he received some support from Thami Tsolekile (20) and Dwaine Pretorius (21).
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