Massive poverty, inequality and falling standards have cost the ANC the retired archbishop's support, he said in an opinion piece carried by the Mail & Guardian.
"I have over the years voted for the ANC, but I would very sadly not be able to vote for them after the way things have gone," the 81-year-old wrote.
"The ANC was very good at leading us in the struggle to be free from oppression," Tutu said of the party which won the first all-race elections.
"But it doesn't seem to me now that a freedom-fighting unit can easily make the transition to becoming a political party," added Tutu, who was discharged from hospital last week following treatment for an infection.
Also Read
Under apartheid, Tutu campaigned against white minority rule and was awarded the 1984 Nobel Peace Prize.
Officially retired but still outspoken on the world's injustices, he is widely viewed as South Africa's moral conscience.
The witty cleric has been increasingly critical of the ruling party in recent years. He accused the ANC government in 2011 of kowtowing to trade partner China when it delayed a tourist visa for buddhist separatist leader the Dalai Lama.
Tutu today also warned that South Africa should prepare for Nelson Mandela's death amid the revered statesman's recent hospital visits.
"He's 94, he's had a rough time, and God has been very, very good in sparing him for us these many years.
"But the trauma of his passing is going to be very much intensified if we do not begin to prepare ourselves for the fact that this is going to happen at some time," Tutu wrote.