"We must make sure when we elect leadership at Mangaung that we bring in a new generation of leadership for radical change," Mashatile, who is also Gauteng ANC chairperson, told the ANC Youth League's 68th anniversary in Thembelihle, south of Johannesburg.
Although it has been speculated for sometime that Mashatile was maneuvering for President Jacob Zuma to be replaced, this is the first time he has openly called for a change in ruling party leaders on a public platform.
"This leadership change in Mangaung will happen, but we must make sure it will happen in a disciplined manner," he said, as the crowd rolled their hands and chanted for a change in ruling party leadership.
Mashatile added the ANC should pursue a major policy shift to bring about immediate change to impoverished South Africans.
"Ownership of the economy must change. We can't just have the right to vote. We need to have economic freedom too. Whoever is elected in Mangaung must bring is this change," he said.
While Mashatile did not mention any candidates by name, ANC Youth League deputy president Ronald Lamola did so in his address.
"We must say without fear that we want Kgalema Motlanthe as our president," said Lamola.
Lamola added that a change in the current crop of ANC leaders was inevitable and that younger leaders should emerge to take the country forward.
"We are not a group of cheerleaders for the ANC. We are a critical group who must ensure the ANC does its job.
"In Polokwane there was no confusion. We told them they'd have five years and then we'd decide in Manguang if they'd return. The ANC must be taken over by a new generation of leadership of young people," he said.
He added South Africa was still divided along racial and class lines.
"We must amend the Constitution to bring radical change."
Lamola also used the occasion to offer a thinly veiled criticism of the ANC's handling of the expulsion of former youth league president Julius Malema. "Our current ANC leadership only speaks about discipline. They don't talk about bringing water or services to the people," he said.
Nominations for new leadership ahead of the ANC December elective conference in Mangaung officially open in October. No senior ANC leaders, including Motlanthe, have indicated their availability.