Carrying a niggling knee injury, the mercurial Australian made a slow start and was forced to save five break points before he managed to carve out own his first break in the seventh game.
The 22-year-old claimed the first set before taking control of the match after his American opponent dropped serve at the start of the second set with a double fault.
Kyrgios broke the big-serving Harrison again in a sublime second set display to close out the match and seal his fourth career title.
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He thrilled the crowd with his delightful touch at the net, while his ability to crank up the pressure with his groundstrokes threw Harrison off his game.
"I've got fond memories of Brisbane, played Davis Cup here and had a massive win over the US," Kyrgios said.
"Coming here all week I felt right at home... I love playing in front of you guys even though sometimes you may not see it that way, but I do."

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Kyrgios became the second Australian to lift the trophy in the tournament's 10-year history after Lleyton Hewitt in 2014.
The triumph lifts him four spots to 17th in the world rankings ahead of this month's Australian Open.

Sealed with an ace - Kyrgios takes Brisbane title in impressive fashion

Kyrgios has often struggled to produce his best tennis at the grand slams, but he goes into the Australian Open having made a strong start to the season, including a semi-final victory over world number three Grigor Dimitrov in Brisbane.
The men's field at the first grand slam of the year has already been hit by the withdrawals of five-times runner-up Andy Murray and Japan's former U.S. Open finalist Kei Nishikori.
The participation of former champions Rafael Nadal, Novak Djokovic and Stan Wawrinka remains in doubt with the trio battling to overcome injury problems.
The Australian Open begins at Melbourne Park on January 15.
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11/01/2022 AT 10:22