By Guy Birchall
The 82-year-old San Francisco representative has been speaker twice during her time in Congress and was the first woman to take the role.
Nancy Pelosi has said she will not run again to be Democratic leader in the House of Representatives, after nearly two decades in the role.
The veteran politician lost the speakership after the Republicans took the House in the recent midterm elections.
Despite saying she would step down from the role she has held since 2004, Mrs Pelosi said she would continue to represent San Francisco in the House, as she has done for 35 years.
The 82-year-old has served as speaker twice during her time in Congress, and was the first woman to take the role when she was elected in 2007.
She revealed her decision in a speech to the House on Thursday and was cheered by her fellow Democrats, who must now choose a new leader.
The favourite to replace Mrs Pelosi as Democratic leader is Representative Hakeem Jeffries of New York.
Now they have the majority, the speakership will likely pass to House Republican leader Kevin McCarthy when the new congress is sworn in on 3 January.
In her speech, she recalled visiting the Capitol for the first time as a child when her father was sworn in as a Congressman.
She described the House chamber as “sacred ground” and called it the “heart of American democracy.”
“I never would have thought that someday I would go from home-maker to House speaker,” she said.
“I will not seek re-election to Democratic leadership in the next Congress. The hour has come for a new generation to lead the Democratic caucus.”
Referencing last year’s attack on the Capitol, she continued: “American democracy is majestic, but it is fragile. Many of us here have witnessed our fragility first-hand, tragically in this chamber. And so democracy must be forever defended from forces that wish it harm.”