The Lions clinched top spot in the South African Conference, and second on the overall Super Rugby table, after a rampant 38-12 bonus-point victory over the Bulls in a frenetic local derby at Ellis Park.
The Johannesburg-based side, losing finalists in the previous two seasons, ensured they would be the second seeds in the quarter-finals behind only defending champions Canterbury Crusaders as they overturned an early deficit to claim a handsome win on Saturday.
They will play the Jaguares at home in the knock-out round next weekend.
Early tries from flyhalf Manie Libbok and Springbok centre Jesse Kriel had put the Bulls into a 12-0 lead, but the Lions began to win the forward battle and wing Ruan Combrinck scored a brace as they roared back into the contest.
They also profited from a penalty try as their scrum pressure in the Bulls 22 forced the error from the visitors, while hooker Malcolm Marx, and wings Courtnall Skosan and Aphiwe Dyantyi, crossed for tries.