Le Clos, 20, who has been in supreme form all week, clocking four A-standard times, won a thrilling 200 metres individual medley race in time of one minute, 58.97 seconds (1:58.97).
The KwaZulu-Natal swimmer was slower than he had been in the semi-finals, but was nonetheless inside the required 2:00.17 mark.
He did show some signs of fatigue later in the evening, though, when he was the fastest qualifier in the 100m butterfly, which he won in 53.43 seconds.
Athens gold medallist Townsend went quicker in the final, dipping under the A-standard time with a 1:59.34 in a race that had additional interest due to Sebastien Rousseau already having a qualifying time prior to the meet.
Rousseau (2:00.37), however, was only third quickest and missed out altogether.
“It’s been a pretty stressful week for me,” Townsend said.
"I’m not used to missing qualification. I usually get the times on my first two swims and I didn’t get them until last night.
“I was glad to get it at the end and it’s a huge relief.”
Another former Olympic gold medallist, and one of South Africa’s most celebrated swimmers, Schoeman produced a stunning swim on his way to the 50m freestyle final.
The 31-year-old, who missed out on an A-standard time in the 100m freestyle, finished in 22.08, edging out Brad Tandy (22.51) and Gideon Low (22.59).
“I’m absolutely ecstatic,” Schoeman said.
“I’ve been so close now for the past seven months and to get it is a big monkey off my back, coming here tonight and swimming that kind of time.”
Prinsloo also set the standard in a semi-final race as she clocked 2:10.74, marginally inside the qualifying mark of 2:10.84 in the 200m backstroke.
That time meant the Northern Tigers swimmer, who already had an A-standard time in the event, assured herself of a place in the SA team for the London Games.
Prinsloo also won the 100m freestyle final, but her time of 55.77 was outside the qualifying mark of 54.57.
The last A-standard time on the night came in the 200m breaststroke final, which was lit up by Van Biljon’s 2:26.74 that came on the back of her semi-final time of 2:25.89.
The only other final that took place was won by Charl Crous as he claimed the 200m backstroke title in 1:59.94.