The Serb will return to world number one as he overcame a hamstring injury and off-court drama to sweep past the Greek third seed 6-3, 7-6 (7/4), 7-6 (7/5) on Rod Laver Arena.
The 35-year-old climbed to his player's box afterwards to embrace his mother and broke down in uncontrollable tears, collapsing to the ground sobbing.
His father Srdjan was again missing after he sparked controversy by posing with a fan carrying a Russian flag featuring Vladimir Putin's face following his son's quarter-final win.
The emphatic victory over Tsitsipas capped a remarkable return for Djokovic to Melbourne Park, having missed last year's tournament when he was deported over his Covid vaccination stance. "I have to say this has been one of the most challenging tournaments I've ever played considering the circumstances, not playing last year, coming back this year," he said at the presentation, wearing a jacket with 22 emblazoned on it. "I want to thank all the people that made me feel welcome, comfortable, to be in Melbourne. "I try to pinch myself and really live through these moments, it's a long journey," he added. "Only my team and family know what we have been through in the last four or five weeks and this is why I'd probably say this is the biggest victory in my life considering the circumstances." There had been an air of inevitability about Djokovic triumphing once more.