"Loyalty should be a two way street" while Congress "has mostly been sidelined" under the Trump administration, Greene posted in a lengthy resignation statement on social media.
The dispute between Trump and the Georgia politician has fuelled concerns among some Republicans that Trump's Make America Great Again base could fracture a year before midterm elections, when Democrats hope to regain control of Congress.
Greene's resignation will narrow the Republican majority in the House to 218 members over the Democrats' 213. Republicans have a 53-47 majority in the Senate.
The White House did not immediately respond to a request for comment on the resignation.
Long a fierce defender of Trump and MAGA, Greene in recent weeks has taken positions at odds with the White House and some of her fellow Republicans, which led the president to withdraw his endorsement of her.
She has cited as a cause for the rupture her advocacy for releasing the government's files on convicted sex offender Jeffrey Epstein. Greene also this year became the first Republican politician to call US ally Israel's assault on Gaza a genocide.
Trump, who had dismissed the Epstein issue as a "Democrat hoax" and has struggled with the uproar in his base over the topic, signed a bill this week to release the documents after it passed the House and Senate with overwhelming support.
In her resignation video, Greene underscored her longtime loyalty to Trump except on a few issues, and said it was "unfair and wrong" that he attacked her for disagreeing.
"I have too much self-respect and dignity, love my family way too much, and do not want my sweet district to have to endure a hurtful and hateful primary against me by the president we all fought for, only to fight and win my election while Republicans will likely lose the midterms," Greene wrote.
"I refuse to be a 'battered wife' hoping it all goes away and gets better," she added.
with AP
