Alexandria Ocasio-Cortez, 28, defeated political veteran Joe Crowley, 56, on Tuesday night in their party's congressional primary in New York City.
Mr Crowley, a 10-term Democrat, had been tipped as a future party leader or even Speaker of the House.
Ms Ocasio-Cortez, a former Bernie Sanders volunteer from a Puerto Rican family, won with 57.5% of the vote.
Mr Crowley had not faced a challenger from his own party in 14 years in the majority ethnic minority district, which covers parts of the Bronx and Queens.
Ms Ocasio-Cortez will now face Republican candidate Anthony Pappas in the November mid-terms.
If she wins, she will become the youngest ever woman elected to Congress.
The political novice, who describes herself as a socialist Democrat, had huge grassroots support. She raised more small-dollar donations than any other New York City congressional candidate.
She led a progressive campaign, supporting universal healthcare, tuition-free college and criminal justice reform.
During her campaign, she criticised Mr Crowley for his ties to Wall Street and accused him of being out of touch with his increasingly diverse constituents.
They thanked each other after the result, with Mr Crowley saying he would support Ms Ocasio-Cortez in the mid-terms.
Who is Alexandria Ocasio-Cortez?
One of the many new female faces joining US politics this year, Ms Ocasio-Cortez is a Bronx-born Latina, a community organiser and educator from a working-class background.
The political newcomer made a viral campaign video in which she said: "I was born in a place where your zip code determined your destiny. Women like me aren't supposed to run for office."
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