Durban - The Lions on Saturday ground out a 27-10 Super Rugby final-round victory over the Sharks to top the overall standings, which guarantees home advantage in every knockout match they play.
The teams clash again next weekend in the quarter-finals of the annual southern hemisphere competition, with the Johannesburg-based Lions playing in front of their supporters.
A try by fullback Andries Coetzee after the hooter sounded for half-time gave the visitors a 13-10 advantage by the break at Kings Park.
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 31-22 at the Hurricanes earlier on Saturday.
The Durban result prevented the Sharks and the Highlanders of New Zealand making long journeys in the quarter-finals.
The Highlanders will travel from Dunedin to Christchurch in the south island to face the 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 the Stormers.
The remaining quarter-final is a trans-Tasman affair with the Brumbies of Australia hosting defending champions the Hurricanes in Canberra.
The Lions or Sharks are likely to be the only non-New Zealand semi-finalists with Crusaders, Chiefs and Hurricanes favoured to win the other last-eight matches.
"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.
Super Rugby quarter-finals:
Friday, July 21
Brumbies v Hurricanes, Canberra - 11:35 (SA time)
Saturday, July 22
Crusaders v Highlanders, Christchurch - 09:35 (SA time)
Lions v Sharks, Johannesburg - 14:30
Stormers v Chiefs, Cape Town - 17:00