Around 300 customs and border protection agents were being deployed to the 3,200km border, alongside the 1,200 guardsmen, as well as new helicopters and other surveillance equipment.
"The border is more resourced and more secure than it's ever been but the work continues and the challenge remains," Alan Bersin, commissioner of the Customs and Border Protection agency, said.
Obama has pledged $600 million in extra funds to support the mission.
Guardsmen will be stationed in California, New Mexico, and Texas, but the largest share - almost half - will go to Arizona.
Arizona recently passed strict local laws aimed at limiting illegal immigration that allow authorities to arrest anyone not carrying identification.
The Obama administration is, however, taking those laws to court on the grounds that protecting national borders is a function of the federal government.
Civil rights and advocacy groups have also filed separate lawsuits against the state's immigration legislation, which is due to go into effect on July 29.
A judge on Monday, ruled that nine Latin American nations - Ecuador, Argentina, Bolivia, Peru, Colombia, Guatemala, Nicaragua, Paraguay and El Salvador - could join Mexico in support of one of the seven lawsuits.
Of the United States' 300 million people, there are believed to be 10.8 million illegal immigrants.