The 33-year-old bowler, who was part of South African squad during the just-concluded home series against India, said it was not an easy decision to take.
"It was an extremely tough decision but I feel the time is right to start a new chapter," he stated in a Cricket South Africa (CSA) release.
"I have a young family and a foreign wife, and the current demanding international schedule has put a lot of strain us. I have to put them first and this decision will only benefit us going forward," he added.
"I have loved every minute that I have played in the Proteas jersey, and I am incredibly grateful to my teammates, Cricket South Africa, and my family and friends for the support over the years.
More From This Section
"I still feel there is a lot of cricket left in me and I am excited for what lies ahead. For now, all of my energy and focus is on helping the Proteas win the upcoming series against Australia," he said.
CSA acting CEO Thabang Moroe lauded Morkel's contribution to South African cricket.
"He has been a regular selection for both the Standard Bank Proteas Test and ODI squads since 2008, having made his debut as far back as 2006," he said.
"He has formed part of the golden era of fast bowlers that have made the South African Test team a champion outfit that is respected throughout the world," he added.
Moroe called Morkel a role model in South African cricket.
"Being a champion fast bowler is one of the most difficult professions in the sporting world. It requires tremendous skill, dedication and perseverance and, by no means least, the courage to bowl through the pain barrier at times.