Murray won 6-7 (6-8) 6-4 6-4 against his American opponent, with No. seed and world No.25 Opelka undone by the British wildcard.
Three years have passed since Murray came to Australia and indicated he was close to retirement because of hip trouble.
There have been highs and lows since then as the three-time grand slam winner has fought to resuscitate his career.
His lone ATP final appearance since that point came at the 2019 European Open in Antwerp, where he beat Stan Wawrinka to land a surprise title.
Now he is back in another title match, for what will be just his fourth final on the main tour since the end of the 2016 season, when he reached world No.1 status.
Opelka is renowned as a big server and duly sent down 20 aces and four double faults, but Murray showed he can compete on that front too with 16 aces and no double faults.
The Scot also won an impressive 88 per cent of points when he landed his first ball in court, and his serve was not broken at any point.
Murray was awaiting the winner of the second semi-final between his fellow Briton Dan Evans and Russian Aslan Karatsev.
Five-time Australian Open runner-up Murray has been drawn to face Georgian Nikoloz Basilashvili in the first round of the grand slam at Melbourne Park next week. He beat the No.23-ranked Basilashvili in round two in Sydney.