His 1-6, 6-3, 6-4, 6-4 victory earned the big Russian a second grand slam crown after his 2000 U.S. Open triumph.
Runner-up here in 2002 and 2004, Safin hugged third seed Hewitt and raised his arms in triumph after crashing an unreturnable serve on the final point.
Hewitt, winner at Wimbledon in 2002 and the U.S. Open in 2001, has now lost the last two Grand Slam finals after he was beaten by world number one Roger Federer in the U.S. Open last year.
The disappointed Australian however will rise to number two in the world after reaching his first home final.
Safin had got off to a slow and nervous start but changed the course of the match in a drama-charged third set, when he staged a stunning comeback after being down 3-0 to Hewitt, who was buoyed by his home crowd on Rod Laver Arena centre court.
Safin had two chances to break Hewitt's serve in the first game of the third set but Hewitt saved both break points and then held his own serve after the Russian made two sloppy errors in a game which typified the early stages of the match.
CONTROVERSIAL GAME
Hewitt in turn broke Safin in a controversial second game of the third set. He set up his first chance when he outfought Safin in a long rally and then hit a forehand winner when Safin failed to put away a smash.
The tenacious Australian exploded in anger when, at deuce, a Safin forehand on the line was called out by a baseline judge but the call was over-ruled by chair umpire Carlos Ramos, who ordered the point to be replayed.
"Don't be a hero here, mate," Hewitt said to Ramos.
Hewitt seemed to be spurred on by the incident and broke Safin, who put a forehand wide at deuce. Hewitt then got a lucky break when he blocked a half-volley past the stranded Safin.
Safin in turn became enraged with his own game and slammed his racket into the court as Hewitt held serve for a 3-0 lead.
Safin then called for a trainer at the change of ends to massage his thighs. He in turn got angry over a corrected line call in the next game, arguing with Ramos in Spanish.
Hewitt desperately scrambled to save a break point in the sixth game but Ramos gave him a code violation for unsportsmanlike conduct when the Australian aggressively pointed his finger at a baseline judge after hitting a forehand winner to get back to deuce.
Safin eventually broke Hewitt when he crunched a backhand winner down the line. After the point he argued again with Ramos, who warned both players they risked a point penalty if there were any further outbursts.
REMARKABLE TURNAROUND
In a remarkable turnaround, Safin then broke Hewitt again in the ninth game for a 5-4 lead when Hewitt served a double fault on Safin's second break point.
The Russian had his big serve back on track and wrapped up the set in just under an hour, with Hewitt calling for his thighs to be massaged at the end of the set.
Safin served 17 of his 18 aces in the last three sets and by the fourth set he was winning most of the long rallies that Hewitt had dominated in the first set.
Safin grabbed the decisive break of serve in the first game of the fourth set when, during a 30-shot rally, he drew Hewitt to the net and whipped a backhand past his 23-year-old opponent.
Safin beat world number one Roger Federer on his 25th birthday to reach the final in a match being hailed as probably the greatest ever played at Melbourne Park.
That win had been sweet revenge for Safin after he was beaten by Federer in last year's final.
