The 6-4, 6-2 win was the third-seeded Australian's fourth title on the ATP tour and his first on home soil.
Carrying a niggling knee injury, the 22-year-old made a slow start but managed to save five break points and claim the first set.
Standing just two points away from his first career final, De Minaur committed a string of errors, including a double fault to concede a set point to Harrison, allowing the world number 47 back into the match.
There was nearly an all-Australian final, but wildcard Alex de Minaur's fearless run ended after a narrow defeat to American Ryan Harrison, who won 4-6 7-6 (7/5) 6-4.
Having risen to world No 17, Nick Kyrgios is in good form going into the first Grand Slam of the year.
He was the lowest ranked player and the youngest to reach the semi-finals of the men's draw in the Brisbane International's 10-year history.
While surprised not to see Tomic in Brisbane, Kyrgios appeared to be the only one not shocked by De Minaur's semi-final berth.
"The way I put myself in some pretty tough situations, came back from a set down three times against three pretty good opponents, that's just confidence mentally but physically as well", he said of his week in Brisbane.
"Coming here all week I felt right at home".
But the delay did nothing to upset Kyrgios's rhythm and he broke Harrison twice more to take the title in one hour and 13 minutes, fittingly winning the title with an ace.
The American found a way to edge the Australian after being on the brink of losing the match in straight sets 4-6 7-6 (5) 6-4.
Yet the Bulgarian looked like extending his unbeaten streak to three matches against Kyrgios at Pat Rafter Arena on Saturday.
The Australian will take his four matches of tournament play to the Australian Open via the detour of two modified-scores evenings (Fast4) this week in Sydney and Melbourne.