A giant rally in Atlanta, Georgia, launched the latest protests in more than 130 cities on Monday, a day after up to 500,000 people marched through Dallas in Texas to maintain pressure on Congress over immigration reforms.
More than 30,000 rallied in Atlanta to kick off the demonstrations.
Organisers expected more than a million people to take part in rallies from New York and Washington on the east coast to Los Angeles in the west.
Joshua Hoyt, director of the Illinois Coalition for Immigrant and Refugee Rights, said: "This is a national movement of justice for the immigrants, the fight for civil rights of our generation.
"The political parties have to understand that this is something that is not going to disappear."
The US House of Representatives has passed legislation that would make illegal entry a crime and step up the construction of a wall on the US-Mexico border.
"This is a national movement of justice for the immigrants, the fight for civil rights of our generation"
Joshua Hoyt, a rights activist
Efforts in the Senate to agree on a compromise bill, that could open the way for many undocumented workers to be legalised, collapsed last week.
Dressed in white and brandishing US flags, 350,000 to 500,000 people in Dallas waved banners saying "United We Stand. We pray for legal status" and "We are not terrorists".
Fifty thousand people gathered for a similar protest in San Diego, California and an estimated 30,000 in St Paul, Minnesota.
The immigration problem is a growing concern for mainstream America in the run-up to mid-term elections in November.
Three-quarters of Americans believe that the government is not doing enough to stop illegal immigration, according to a poll released on Monday by The Washington Post and ABC television.
But the authorities also acknowledge that the migrants do low-paid "dirty" jobs that many Americans spurn.
Bush called for both compassion
and enforcement of law
On Monday, George Bush, the US president, whose own proposed "guest worker" programme has failed to overcome a split in his Republican Party, called both for compassion and for enforcing the laws over immigration.
"Understand that we're a nation of immigrants, that we ought to be compassionate about this debate," he said, while adding "Obviously, we've got to secure the border and enforce the law."
Most of the illegal workers in the United States are from Mexico and other Latin American countries and many Hispanic families are taking their children on the protests.
Berta Sanchez, a Salvadoran in a Washington suburb, who gained legal status after working in the country illegally for nearly 20 years, headed for the rally with her husband and two children.
"I am going to support my people. We also did not have papers and it was very difficult. We want to show that we are united, whether we have papers or not," she said.
Manuel Cruz, an undocumented immigrant for 11 years who does construction work, said he wanted legal status.
His wife, Maria Rosa, said: "The work we do is heavy, most Americans do not want to do it, they prefer to sit at their computers."
Organisers hope to better protests in late March which they said drew 1.5 million people on to the streets. At least 500,000 protested on March 25 in Los Angeles.
Immigration problem is a concern
for mainstream America
The new protests have "incredible importance", said Eliseo Medina, head of the Service Employees International Union and one of the organisers of a march to be held in New York.
"We march in the streets, but we will also march to the voting booth in November," said Medina, who said that not all immigrants were undocumented and that many would vote.
On Friday, the US Senate failed to approve compromise legislation that would have allowed millions of undocumented workers to normalise their status. The chamber has now gone into a two-week recess.