The world champions are withdrawing two weeks before kick-off, citing player welfare concerns and logistical difficulties after Covid-19 made it harder for international players to travel.
World champions South Africa will not take part in the Rugby Championship in a decision that leaves the tournament greatly diminished two weeks before kick-off.
South African Rugby Union (SARU) said on Friday "player welfare" concerns and logistical difficulties left them no choice but to pull the defending champions out of the competition which also features Australia, New Zealand and Argentina.
"It seems impossible that the Springboks won’t play a test match in 2020, but public health and safety have been the primary concern and we have been hit by collateral damage like so many businesses," SARU Chief Executive Jurie Roux said.
The annual test tournament was already delayed by the Covid-19 pandemic and is being staged in one country for the first time.
It will now consist of six tests, starting with the third Bledisloe Cup clash between hosts Australia and New Zealand in Sydney on October 31.
South Africa-based players only began playing competitive rugby at the weekend after a 29-week hiatus and the SARU was also concerned that 24 overseas-based players might not be able to join the squad.
Australia and New Zealand completed domestic tournaments weeks ago and launched their test season over the weekend.
Argentina, most of whose players have had no match preparation, are already training in a bio-secure hub in Sydney.
South Africa's withdrawal will mean a hit to the tournament's revenue at a time when the participating nations are battling financial challenges brought by the pandemic.
"Clearly it has financial implications ... and the broadcast implications of that are still to be worked through," Rugby Australia (RA) boss Rob Clarke told reporters.
"A bit more notice would have been welcome, there’s no doubt about that. But I know how difficult these things are."
RA, in particular, are under pressure as they look to land a new TV rights deal for 2021 and beyond, but more broadly the decision raises concerns about the long-term future of southern hemisphere rugby.
It will be the first time since 1994 that South Africa will pass a year without playing both Australia and New Zealand, with the three nations launching the Tri-Nations as a joint venture in 1996 and welcoming Argentina into the fold in 2012.
South Africa have long considered the idea of throwing in with the northern hemisphere due to the lucrative European TV market, easier logistics and a more favourable time-zone.
Last month, SARU voted to pull its four major franchises from Super Rugby, the southern hemisphere's provincial competition, and explore expanding their presence in the European PRO14.
Clarke denied the southern alliance was fracturing.
"This isn’t a normal year," he said. "South Africa has expressed overtly its commitment to the TRC into the future."
Northern hemisphere sides are to play in the new Autumn Nations Cup in Europe in November, with the 2021 Six Nations to start in February.
South Africa, however, face hosting the British & Irish Lions on home soil next July without playing a test since their victory in last year's World Cup final in Japan.
Wallabies coach Dave Rennie said the Springboks' absence was disappointing for the competition and for his players.
"If they're not coming, obviously there are less games and less opportunity for some of our young guys to get a taste of Springbok footy," he told reporters.
New Zealand coach Ian Foster said he understood the decision but was more focused on preparing for the second Bledisloe Cup test against Australia at Eden Park on Sunday.
"We understand the pressures on them and the challenges they've had, so what happens, happens," he said.