The Lions ensured they will play all their play-off matches at home, after beating the Sharks 27-10 in Durban on Saturday.
It means the Lions overtake the Crusaders at the top of the tournament's standings and will host the Sharks in the quarterfinal at Ellis Park next week.
Should they advance, the Lions will also host a semifinal and possible Final in the next three weeks.
The Durban result prevented the Sharks and the Highlanders of New Zealand making long journeys in the quarterfinals.
Highlanders travel from Dunedin to Christchurch in the South Island to face Crusaders, who had won 14 consecutive matches this season - before losing in Wellington.
Another New Zealand outfit, the Chiefs, do have to travel far, though, from the North Island to Cape Town for a showdown with Stormers.
The remaining quarterfinal is a trans-Tasman affair - with the Brumbies of Australia hosting defending champions Hurricanes in Canberra.
In a scrappy game in Durban in which the Lions seldom got out of second gear, they outscored their hosts by three tries to one.
The result was never in doubt, as the Lions always seemed to have an extra gear when they needed to.
A try by fullback Andries Coetzee after the hooter sounded for half-time gave the visitors a 13-10 advantage by the break.
The Lions kept Sharks scoreless in the second half of a scrappy match while adding 14 points from a try and three penalties to make it 14 wins in 15 regular-season matches.
They finished with 65 points, two more than long-time leaders, THE Crusaders, who fell 22-31 TO THE Hurricanes earlier Saturday in a New Zealand derby.
"It is an amazing feeling to finish top of the overall standings," said Lions skipper and loose forward Jaco Kriel, who was among the try scorers.
"Our preparations this week were normal with nothing special despite the match in Durban having huge significance.
"What we must not assume is that our match against the Sharks next weekend will be similar to the one we have just played.
"They will be a much more difficult 'monster' to tame even though we will enjoy home advantage at Ellis Park."
Kriel is deputising for No.8 Warren Whiteley, who suffered a pelvic injury in a Test against France last month and is not expected to play again in Super Rugby this season.
Sharks skipper and loose forward Philip van der Walt said a lack of possession, particularly during the second half, prevented his team seriously challenging the Lions.
"Without the ball we were toothless and the Lions were good at keeping us in our own half of the field.
"There was a huge turn-out of our supporters tonight and it is not nice to let them down. We have another chance next weekend and I hope we make the most of it."
Flyhalf Garth April defied a swirling wind to kick an early penalty and give the Sharks a lead they surrendered when hooker Malcolm Marx was credited with a pushover try.
Lions playmaker Elton Jantjies extended the advantage to five points via a penalty, but his careless drop-out gifted winger Kobus van Wyk a try and April converted for a 10-8 lead.
Slick handling by backs and forwards allowed Coetzee to regain the lead for the visitors and Jantjies slotted three second-half penalties and Kriel scored a try.
While leading Super Rugby points scorer Jantjies did contribute 12 points, he suffered the unusual embarrassment of failing to convert any of the three tries.
Man of the match: Despite being know for their attractive brand, it was not the backs, but rather the Lions' forwards that stole the limelight. Loose forward Albertus Smith and captain Jaco Kriel were the most productive - especially at the breakdown. And Smith wins our award.
For the Sharks:
Try: Van Wyk
For the Lions:
Tries: Marx, Coetzee, Kriel
Pens: Jantjies 4
Sharks: 15 Lwazi Mvovo, 14 Jacobus van Wyk, 13 Lukhanyo Am, 12 Andre Esterhuizen, 11 Sibusiso Nkosi, 10 Garth April, 9 Jacobus Reinach, 8 Daniel du Preez, 7 Jean-Luc du Preez, 6 Philip van der Walt (captain), 5 Stephan Lewies, 4 Etienne Oosthuizen, 3 Coenraad Oosthuizen, 2 Mahlatse Ralepelle, 1 Thomas du Toit.
Replacements: 16 Stephan Coetzee, 17 Juan Schoeman, 18 Lourens Adriaanse, 19 Jean Droste, 20 Lubabalo Mtembu, 21 Michael Claassens, 22 Curwin Bosch, 23 Jeremy Ward.
Lions: 15 Andries Coetzee, 14 Ruan Combrinck, 13 Lionel Mapoe, 12 Harold Vorster, 11 Courtnall Skosan, 10 Elton Jantjies, 9 Ross Cronjé, 8 Ruan Ackermann, 7 Albertus Smith, 6 Jaco Kriel (captain), 5 Francois Mostert, 4 Andries Ferreira, 3 Ruan Dreyer, 2 Malcolm Marx, 1 Jacques van Rooyen.
Replacements: 16 Armand van der Merwe, 17 Corne Fourie, 18 Johannes Jonker, 19 Lourens Erasmus, 20 Cyle Brink, 21 Francois de Klerk, 22 Rohan Janse van Rensburg, 23 Sylvian Mahuza.
Referee: Marius van der Westhuizen (South Africa)
Assistant referees: AJ Jacobs (South Africa), Cwengile Jadezweni (South Africa)
TMO: Johan Greeff (South Africa)