Demonstrators gathered in Central Park at Fifth Avenue and 58th Street to mark "A Day Without a Woman".
Women dressed in red and waved signs reading "Nevertheless she persisted," ''Misogyny out of the White House now" and "Resist like a girl."
Several thousand women were quickly on the move, walking to the Trump International Hotel at Columbus Circle to send the president a clear message.
"Hey hey ho ho, Donald Trump has got to go," they chanted. After a brief sit-in, 13 of them were arrested.
In Lower Manhattan, a statue of a young girl with a look of resolve was placed in front of Wall Street's famous charging bull.
Women's March on Washington, the same group that organized the nationwide march the day after the inauguration, has encouraged women to "strike."
The organization is calling it "A Day Without a Woman," and is encouraging women to skip work and unpaid labor at home, or wear red.
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Spokeswoman Cassady Findlay said organizers for "A Day Without a Woman" were inspired by the recent "Day Without an Immigrant" protests held last month.
She said the action is aimed at highlighting the effect of women on the country's socio-economic system and demonstrating how the paid and unpaid work of women keeps households, communities and economies running.
"We provide all this value and keep the system going and receive unequal benefits from it," Findlay said.
Findlay said it is important for white women to be in solidarity with minority women.
"Throughout history, the strikes that have the biggest impact are the ones when people who are already the target of oppression participate," she said. "It's when women of all backgrounds strike and stand together that we're really going to see the impact."
"A Day Without a Woman" coincides with the U.N.-designated International Women's Day.
At 4 p.m. Wednesday, there will be a rally at Washington Square Park, followed by a 5:30 p.m. march to Zuccotti Park. The International Women's Strike NYC rally and march is expected to continue until 8 p.m.
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Musical and artistic performances are planned before the march to Zuccotti Park. The march will stop at the Triangle Shirtwaist Factory, the famous Stonewall Inn, the Immigration Court, Trump Hotel Soho, and the African burial ground on the way downtown.
The International Women's Strike also is hosting a day of activities, including self-defense classes and art classes.
International Women's Day rallies are planned in New York, Philadelphia, Baltimore, Milwaukee, Washington and Berkeley, California.
Some businesses and institutions have said they will either close or give female employees the day off.
School districts including Prince George's County in Maryland, the Alexandria City Public Schools in Virginia and Chapel Hill-Carrboro Schools in North Carolina have canceled classes in anticipation of employee participation. In Utah, as many as 1,000 women are expected to gather at the Capitol to remind lawmakers they are watching their actions on women's issues.
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"Strike houses" also are opening their doors to women striking, encouraging them to spend the day together.
Female Democratic congresswomen are hosting solidarity rallies in Washington in the afternoon, one on Capitol Hill and at the Department of Labor.
President Trump took to Twitter on Wednesday and asked followers to join him in "honoring the critical role of women" in the U.S. and around the world. He tweeted that he has "tremendous respect for women and the many roles they serve that are vital to the fabric of our society and our economy."
Ivanka Trump echoed her father's sentiments, tweeting: "Today, we celebrate women and are reminded of our collective voice and the powerful impact we have on our societies and economies."
The Associated Press contributed to this report.