The 20-year-old dipped inside the Olympic mark in four of the five races he entered and was among nine athletes who secured trips to London.
The highest profile name to guarantee selection was breaststroke specialist Cameron van der Burgh in the 100 metres.
Darian Townsend (200m individual medley), Riaan Schoeman (400m individual medley), Gideon Louw (100m freestyle) and Heerden Herman (1500m freestyle) were the other men to achieve qualifying times.
Kathryn Meaklim (400m individual medley) was one of just three women to make the team, along with Wendy Trott (800m freestyle) and Karin Prinsloo (200m backstroke).
Le Clos, the 2011 FINA World Cup Series winner, achieved qualifying times in the 200m individual medley, 400m individual medley, 200m freestyle and 200m butterfly.
The Durban-based swimmer played down his medal hopes in London.
"Obviously, I understand there's going to be a lot of expectation after these trials, but for me personally I know that 2016 will be my main Olympics," he told reporters.
The SA Sport Confederation and Olympic Committee (Sascoc) has set stringent qualifying standards for its team in the wake of their failure at the Beijing Olympics when the team failed to scoop any medals in the pool.
Sascoc requires all Olympic hopefuls to swim below the QT twice during a 10-month period, including once during the national trials.
There were also a few athletes that did swim inside the Olympic mark for the first time, but they now need to compete at a meet in Europe before the May 15 cut-off to complete Sascoc's criteria.
Roland Schoeman, the country's most successful Olympic swimmer in terms of medals, tops that list after he had a QT time in the 50m freestyle, while the other two are Charl Crous (100m backstroke) and Suzaan van Biljon (200m breaststroke).
The team is expected to be finalised soon after the cut-off date next month.