The South African women's 4x100m medley relay team of Charlene Wittstock, Sarah Poewe, Mandy Loots and Helene Muller set a national record of 4:07,19 in the heats to earn a spot in Saturday's final.
"I'm in the best race of the meet - the relay," said Poewe, swimming in place of recently-retired Penny Heyns.
"The pressure's hard and we're not cracking. That's a good thing," added Helene Muller, who earlier failed to qualify for the women's 50m freestyle semifinals after clocking 26,07.
South African distance swimmer Ryk Neethling on Friday qualified fourth fastest for the 1 500m freestyle final, clocking 15mins 09,12secs to finish second in his heat behind Australia's Grant Hackett (15:07,50).
Australian world record-holder Kieren Perkins was fastest in 14:58,34 and Eric Vendt of the US next best in 15:05,11.
Neethling was happy with his time, although he would have preferred to have won a lane alongside the Australians for Saturday's final.
"It's going to be a fast final," pointed out Neethling, who finished fifth at the Atlanta Games four years ago.
"To get any kind of medal, one's going to have to swim 14:50, I think."
The men's medley relay outfit of Simon Thirsk, Brett Petersen, Theo Verster and Nicholas Folker were unable to qualify for the final in their event, managing only the 13th best time of the morning.
No South Africans will be competing in Friday's finals.
Meanwhile, Friday saw a major triumph for South African rowing when the men's lightweight coxless fours team of Mark Rowand, Ross Hawkins, Roger Tobler and Mike Hasselbach came third in their semifinal to qualify for the final, thus emulating the men's and women's coxless pairs. All three will be racing in the early hours on Saturday.
In boxing, South African lightweight Phumzilke Matyhila was on Friday outclassed by Kenya's Suleiman Bilali.
On Thursday, in the space of 10 minutes in the pool, Brendon Dedekind and Roland Schoeman were eliminated from the men's 50m freestyle at the semifinal stage, while Sarah Poewe finished sixth in the women's 200m breaststroke final.
Helene Muller later proceeded to swim the fastest 100m of her life, but another national record for her at these Games, this time 55,19 seconds, was only good enough for sixth position in the final.
In rowing, the men's coxless pair of Ramon di Clemente and Donovan Cech finished third in their semi to reach the final.
Young sailor Gareth Blanckenberg finished 33rd in the third open Laser fleet race, but came back for a creditable sixth spot in the fourth, a minute adrift of Brazilian winner Robert Scheidt. The 5th and 6th races are on Saturday.
On the shooting range, Jaco Henn and Corne Basson disappointed in the men's 50m rifle prone qualification round, Henn scoring 585 points for 44th place out of 53 and Basson shooting 583 for 47th spot.