Ko carded a final round of 68 at Royal Greens Golf and Country Club on Sunday to finish 21 under par, a shot ahead of India's Aditi Ashok.
American Lilia Vu had taken a one-shot lead over Ko into the final round but could only card a closing 71 to share third place with compatriot Lexi Thompson and Belgium's Manon De Roey.
"I'm two for two on this golf course so clearly something is going for me," said Ko, who won the title in 2021 but did not defend it last year.
"I don't think I was setting myself up for a lot of birdie opportunities on the front nine, but I knew that every hole could be a birdie opportunity, so it was that kind of mindset and I wanted to be aggressive.
"In the end, it's definitely nice to get the win this week."
Ko picked up the richest prize among regular Ladies European Tour events, taking home $US750,000 ($A1.1 million) from the $US5 million ($A7.3 million) prize fund.
She ended last year by winning the LPGA Tour finale, which elevated her to No. 1 in the world, and got married in December, skipping the LPGA Tour's season opener in Florida last month before returning to win this 26th title of her career.
Defending champion Georgia Hall finished seventh on 16 under par following consecutive rounds of 67 over the weekend.
Sydneysider Steph Kyriacou, the only Australian to make the cut, ended up 50th after a final round of 74.
With AP