Middlesbrough striker McDonald, a prolific goal-getter at club level in Scotland for both Motherwell and Celtic before moving to Teesside, has not scored in 16 appearances for the Socceroos.
The 26-year-old failed once more in Monday's fortuitous 2-1 win over New Zealand, prompting coach Pim Verbeek to include him in a three-man cull which saw the party reduced to 28. Defender Jade North and midfielder Nick Carle were the other men to miss out on the plane to South Africa.
Verbeek has sought permission from Football Federation Australia to allow youngsters James Holland and Tommy Oar and fourth keeper Eugene Galekovic to travel with the team to South Africa but they will not be considered for World Cup selection unless another player is injured.
That 28-man squad will fly out on Wednesday with Verbeek set to name his final 23-man group on June 1 when Australia play Denmark in the first of two friendlies in South Africa prior to their first World Cup group game against Germany in Durban on June 13.
While the axing of North and Carle - neither of whom featured even amongst the substitutes against the Kiwis - was no surprise, the axing of McDonald is a major shock.
It means the Socceroos squad now contains just three front line strikers in Josh Kennedy, Harry Kewell and the little known Nikita Rukavytsya - who has just two caps - although Brett Holman - who scored the winning goal against New Zealand - can also play as a striker if needs be.
And with Kewell (groin) and Kennedy (back soreness) currently injured, the axing of McDonald leaves Verbeek with few options if that key pair do not recover in time to face Germany.
Source: PA
