A second-string Lions team crumbled in Buenos Aires after they went down 34-22 to Jaguares in their final game of the regular season, handing first place to Hurricanes in Super Rugby.
Lions required a bonus point from their trip to Argentina's capital on Saturday to secure top spot but the South African franchise faltered in the second half as Hurricanes finished top of the standings by a solitary point.
Johan Ackermann's Lions led 15-12 at half-time only to be outscored 22-7 following the break as Jaguares won for the fourth time in their debut campaign, though the South African visitors still retained home advantage for next week's quarter-final showdown against Crusaders.
Top seeds Hurricanes will host Sharks and Brumbies will welcome Highlanders to Canberra.
Stormers are set to take on Chiefs after they dismantled Kings 52-24 thanks to four tries from Huw Jones and three from Leolin Zas.
Bulls, meanwhile, accounted for Cheetahs 43-17.