The American began the final day with a three-shot lead but won by one shot from South Korea's Chun In-gee.
Lewis carded a 69 in her last round in Oregon to finish on 20-under, while In-gee shot a 66.
"We're going to be able to help people rebuild houses and get their homes back. That's more important than any win," said Lewis.
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The victory was her first LPGA Tour title since 2014.
She had pledged to donate her winnings to the relief effort following Storm Harvey in Houston, where she and her husband have a house, prior to the tournament.
Lewis was also told one of her sponsors would match her donation.
Stacy Lewis donated her £150,000 prize money to the flood victims in Houston after winning the Portland Classic.