Supporters of the Day Without Immigrants stayed away from work, kept children out of school and stopped shopping on Monday in protest at a new law that makes illegal entry into the US a full criminal offence.
Food production companies which employ large numbers of mainly Hispanic immigrants on low wages were hardest hit by the day's strike.
In the Los Angeles area – where more than one million people were expected to march in support of immigrant's rights - restaurants and markets were closed and truckers avoided the nation's largest shipping port.
Food giants Tyson and Cargill said they had closed about 20 meat-packing plants, and in California and Florida fields remained empty as farm workers stayed at home.
"I want my children to know their mother is not a criminal," said Benita Olmedo, a Mexican nanny who illegally entered the US in 1986, at a rally in San Diego.
In Chicago, more than 300,000 people marched for miles, waving flags and pushing prams.
"I came to this country because its freer than where I came from ... and we need to keep it that way"
Major demonstrations also took place in Denver, Houston, San Francisco and many other cities.
In New York City, demonstrators formed "human chains" at several points around the city.
Thousands also marched in Mexico and across Central America in solidarity with their compatriots who make up the bulk of the undocumented immigrants.
Hatem Zahdan, a Kuwaiti immigrant, joined a group of Muslims at the Chicago rally.
"I came to this country because it's freer than where I came from ... and we need to keep it that way," he said.
Not all immigrant's rights groups supported the strikes and the We Are America coalition, which includes the Roman Catholic church, encouraged people to go to school and work and then join the demonstrations later in the day.
Reaction to the protests from the US business community was also mixed.
Protests also took place in
central New York
Cargill and Tyson have said they understand the reasons for the action by immigrants.
But other firms complained that their businesses had been affected by the strike at the busiest time of the year.
Illegal immigrants, who flood across the Mexican border at a rate of half a million a year, work mostly at low-paid jobs in agriculture, construction, restaurants, as caretakers, meat-packers, maids and gardeners and many other occupations.