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 on Saturday.
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 Crusaders as they overturned an early deficit to claim a handsome win.
They will play the Jaguares at home in the knock-out round next weekend, while the Hurricanes host the Chiefs in an all-New Zealand clash and the Waratahs entertain the Highlanders.
The Crusaders will host South Africa's Sharks after they beat a second-string Jaguares side to win a place in the playoffs.
Early tries from flyhalf Manie Libbok, who was a late replacement for Handré Pollard, 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 in the second half forced the error from the visitors, while hooker Malcolm Marx, and wings Courtnall Skosan and Aphiwe Dyantyi, also crossed for tries.