Charlene met Prince Albert at the Mare Nostrum swimming competition in Monte Carlo, Monaco, in 2000.

Princess Charlene's charity work primarily revolves around sports, AIDS, and underprivileged children.

She represented South Africa at the 1998 and 2002 Commonwealth Games, winning a silver medal in the 4 × 100 m medley relay in the latter competition.

[2] She left her Durban-based team (the Seagulls) to join the Tuks Swimming Club at the High Performance Centre of the University of Pretoria.

On 13 April 2007, Wittstock regained her title as South Africa's 50-metre women's backstroke champion when she completed the 50 m backstroke final at the Telkom SA National Aquatic Championships in 30:16 seconds, to finish third behind Australia's Sophie Edington and Brazil's Fabíola Molina.

[32] She has stated that the movement is close to her heart as a former athlete and values its role in "using the power of sport to change lives".

[32] In July 2011, she became a co-patron of Giving Organizations Trust, a group of South African charities that work with AIDS, underprivileged children, and environmentalism.

[2] In September 2014, she formally presented her foundation at the 10th Annual Clinton Global Initiative Meeting in New York City.

In November 2015, Charlene partnered with the Pontifical Council and attended the 20th Annual Conference for Healthcare Workers at the Vatican, where she spoke about efforts against the global drowning epidemic.

She visited the Olympic Village and sports facilities in conjunction with government officials, and later donated a travel bus to the Tbilisi Rugby Club Team.

She also took meetings with Paralympic athletes and visited the Ai la foundation, a rehabilitation centre for children with hearing loss.

[36] In January 2024, Charlene became the honorary president of Pink Ribbon Monaco, a campaign for the fight against breast cancer.

[38] A month later, Princess Charlene and Prince Albert visited Paris to attend the opening ceremony of the 2024 Summer Olympics.

[39] In May 2021, while on a trip to raise awareness about the issue of rhinoceros poaching in Southern Africa, Princess Charlene caught an ear, nose, and throat infection.

[43] Subsequently, she missed the tenth anniversary commemorations of her marriage in June, which Charlene stated was "extremely difficult" and saddened her.

[47] On 16 November 2021, the palace announced that Charlene would be resting and that she had cancelled all her activities, including those of Monaco's national celebrations, owing to ill-health, especially "deep fatigue".

[49] After a four-month stay at a Swiss clinic, the palace stated in March 2022 that Charlene was back in Monaco with her family and was expected to restart her duties gradually as her health further improved.