The protestors wanted to show their importance to America’s economy and demanded reforms aimed at helping more than 11 million illegal workers gain legal status.
Many companies that rely on low-wage Hispanic labour were forced to close factories, while immigrant-owned stores across the country shut for the day.
In Chicago, more than 300,000 people marched through the
streets as cheers, songs and the beat of drums drowned out the sound of cars honking in support.
A seemingly endless sea of people held signs calling for amnesty for illegal immigrants and an end to deportation, raids and uncertainty.
They waved placards bearing the words "we want to pay taxes" and "we want to own homes" in Spanish and "Today we March, Tomorrow we Vote."
Education authorities in Chicago estimate up to 30 percent of
students skipped classes as part of the protests called "Day Without Immigrants."
While the bulk of the crowd was Hispanic, unions, church groups, a handful of green-clad "Celts" and a group of about 150 Korean, Chinese and Filipino students also joined the protest.
"To those who think we can simply close off the borders and deport, let me say this: there is no reason to fear people who have come here for the same reason as generations of Americans," said one protestor.
There was a much smaller protest in Florida where about 20,000 people took to the streets of Orlando while thousands more took part across the state.
In Orlando, a few hecklers yelled at the protesters demanding they return to their home countries, bearing signs telling the immigrants to "March back to Mexico."
Police arrested one man, John Butler Book, 37.
Book is an ultra-conservative former pastor, who runs a nationally syndicated talk show and is known for his virulent protests against such issues as gay rights, abortion and immigration.
"He was arrested for trespassing and resisting arrest," said Orlando police spokeswoman Sergeant Barbara Jones, pointing out the organisers had rented the downtown space where the rally began.
Chanting in Spanish: "We are not leaving; if they kick us out we'll come back," the demonstrators drowned out the voices of the handful of hecklers, some of whom were led away by police.
In nearby Miami, thousands of demonstrators packed the parking lot of the Orange Bowl sports arena, swaying to Latin tunes and cheering speakers who called for more rights for the workers.
Many waved flags from their nations of origin as well as the US Stars and Stripes. The colours of Mexico and central American nations were displayed prominently, as were Cuban flags.
LA brought to standstill
In Los Angeles, tens of thousands of protesters marched through the city in a noisy but peaceful protest that brought traffic to a grinding halt.
Aerial photos showed block upon block of the city centre flooded with protesters, while the city's usually snarled freeways were virtually free of traffic.
Many of the protestors wore white and waved US and Mexican
flags in this city with a population that is almost half Hispanic.
"I'm fighting for the working people because I think it's their right to be here," said Maria Flores, 62, who moved to Los Angeles from her native Mexico City in 1960 and later became a legal citizen.
The demonstrations also shutdown the normally bustling port of Los Angeles, which was instead eerily silent as truck drivers joined the boycott and stayed away from work.
Limited support from business
Major American companies that rely on cheap labour took a surprisingly supportive view of the army of workers taking part
in immigrant rights protests on Monday.
Immigrant workers were in turn, however, nervous about taking part in a strike, which they had feared could see them lose their jobs.
Fast good giant, McDonald's, paid tribute to its foreign workers
and said it "strongly supports" immigration reform.
"Immigrants have contributed to the growth and prosperity of our nation and they deserve to be treated with respect and dignity," it said in a statement.
"Some of our employees may be participating in today's activities. We respect their right to do so. To meet our customers' needs, some of our restaurants may be operating with limited crew, limited hours or drive-thru service only," it warned.
Food giants such as Tyson Food Inc. and Cargill Foods said they would close about 20 plants between them on Monday.
Goya Foods announced a complete halt to daily distribution.
Gallo Wines in California said it also closed some operations because of the protests.
All the companies said they understood the sentiments behind the protest.
"We share many of the same concerns about some of the proposals in Washington," said Cargill spokesman Mark Klein.
Some employers groups were not so happy and gave only begrudging backing.
The National Council of Chain Restaurants (NCCR) said the strike and boycott of schools "could hurt companies that have been vocal advocates of treating illegal workers fairly through comprehensive immigration reform in Congress".
"No one understands how vital immigrants have become to America’s economy better than the chain restaurant industry", said Scott Vinson, Vice President of Government Affairs for NCCR.
"Unfortunately, these work boycotts have the potential to handcuff the very businesses that have worked so hard for immigration reform."
But many firms organised a Tuesday-to-Saturday workweek to lessen the impact of the protests, which brought more than a million people onto the streets.