Ana Ivanovic evened the tie by overwhelming Australian teenager Ashleigh Barty 6-2, 6-3. Barty made a positive start, but once Ivanovic made the first break to lead 4-2 she took almost total control to ensure the tie would be decided in the mixed doubles.
Tomic put Djokovic under pressure right from the start, holding five break points in the opening game. Djokovic survived that threat and held a break point of his own to lead 5-3 but netted a backhand. Tomic then broke serve in the next game with a crosscourt forehand winner and served out the set.
He kept up the pressure in the second set, failing to convert a break point to lead 4-3 but won his sixth break point at 5-4 which left him serving for the match, and his first win over Djokovic in four tries.
"I played a very, very good match and I'm just happy after the training the last few months, that it's all coming good and the training's paying off," Tomic said.
"Hard work does pay off. I'm still improving but I feel this today was a very good sign. I've got to continue playing like this."
Playing in front of more than 13,000 in the sold-out arena, Tomic admitted to feeling nervous at the start.
"Very difficult to play the first few games," he said. "It's very hard playing against a player like Novak and come out relaxed. But I'm happy the way I came out. I was serving really good and the whole match was on my side because my serve was working really well."
Djokovic was generous in defeat and conceded that Tomic deserved his victory.
"He played really well. He deserved to win," Djokovic said. "I knew I was coming here to Australia really late and it still takes time for me to get used to it.
"But I'm not taking anything from his win. He played terrific. He's in great form. I was always on the back foot and he was the better player."
Earlier, Italy came from behind to beat Germany 2-1.
Francesca Schiavone staged a fightback to defeat Tatjana Malek 3-6, 6-3, 6-3 and level the tie for Italy after Tommy Haas resisted a solid challenge and defeated Andreas Seppi 7-6 (3), 7-6 (7). Italy then won the doubles 6-4, 7-5.
On Thursday, the United States team of John Isner and Venus Williams plays the Spanish pairing of Fernando Verdasco and Anabel Medina Garrigues for a place in Saturday's final. Australia also face Italy.