The South African leader may play a role in the Mideast
He said the US and Europe's former colonial powers had sent the wrong message by dispatching only junior delegations.
Mr Mbeki's criticisms came as the US and Israeli delegations threatened to walk out over what they say is discrimination against Israel.
However, moves by Norway for a compromise declaration may yet calm emotions.
Mr Mbeki told the Reuters news agency that the US was responsible for letting the Middle East dominate the conference.
The US had "aggressively lobbied" on Israel's behalf in the run-up to the conference and delegates had been "forced to make statements in order to assert which side they are on in this particular debate".
Having caused so much friction, Mr Mbeki said, Washington could not just announce: "Well, I'm not going to come".
Muted anger
A member of the US delegation, Democrat Congressman Tom Lantos, said that the US was likely to walk out if the row over the Middle East issue was not resolved "in 24 to 36 hours".
As the BBC's Nick Childs reports from Durban, Congressman Lantos said that extremists were turning the gathering "from a conference against discrimination into one of discrimination, by singling out Israel for attack".
Mr Lantos later said that the wording of a draft declaration by Norway, which heads the conference group on the Middle East, suited Washington.
"If the conference, and it still has a chance, will refocus on its original goals and objectives, it can still be rescued," he said.
But he warned that the conference could still be wrecked by "those whose only goal is to gain a cheap political advantage, a propaganda gain at the expense of the state of Israel".
Mr Lantos said many delegates to the conference agreed with him but were afraid to speak out.
Role for Mbeki
The Israeli delegation was saying on Saturday that efforts to remove anti-Israeli language from the final declaration had so far failed.
It said it was reaching the stage where it would have to consider walking out.
In another development, South African newspapers are saying President Mbeki may shortly play an important role as a Middle East negotiator.
Mr Mbeki has had separate talks in Durban with Palestinian leader Yasser Arafat and Yossi Beilin, a former Israeli cabinet minister.
Mr Beilin said that South Africa was in a "unique position to play a constructive role in ending the Middle East conflict".
Mr Mbeki and his government "were trusted by the Palestinians and 'not distrusted' by the Israelis," he commented.