"I reckon this might be the toughest qualifier for the World Cup," the West Ham defender said.
"We are going into the unknown to play a team we know very little about in an environment we are not used to," he said.
"We simply do not know what we are coming up against and it’s going to be a great experience and challenge."
With most of the Socceroos based outside Australia, Neill said away wins were crucial. This is because home games are actually "away" games for many of the players, meaning that Australia do not benefit so much from home advantage.
Australia keeper Mark Schwarzer said the little he knew of Uzbekistan suggested a tough match.
"We saw a little bit of them at the Asian Cup last year - they looked a pretty good side," he said.
"They're going to be a very, very difficult game for us away."