The Senate bill includes numerous steps to prevent future illegal immigration, while at the same time offering a chance for citizenship for the 11 million undocumented immigrants now living in the United States.
It provides for 20,000 new Border Patrol agents, requires the completion of 700 miles of fencing as well as an array of high-tech devices to be deployed to secure the border with Mexico.
Also, businesses would be required to check on the legal status of prospective employees. Other provisions would expand the number of visas for highly skilled workers relied upon by the technology industry. A separate program would be established for low-skill job workers, and farm workers would be admitted under a temporary program.
The bill faces tougher opposition in the House of Representatives. Many House conservatives are opposed to the bill.
A series of test votes this week showed that supporters have a bipartisan majority well over the 60 votes needed to secure passage and send the bill to the House.
Supporters posted 67 votes or more on each of three tests on Wednesday. More than a dozen Republicans sided with Democrats on each test, ensuring bipartisan support that the bill's backers hope will change minds in the House.
In a written statement, Obama coupled praise for the Senate's action with a plea for resolve by supporters as the House works on the issue. "Now is the time when opponents will try their hardest to pull this bipartisan effort apart so they can stop commonsense reform from becoming a reality. We cannot let that happen," said the president, who was traveling in Africa.
The basic legislation was drafted by four Democrats and four Republicans known as the "Gang of Eight" who met privately for months to produce a rare bipartisan compromise in a polarized Senate.
In the House, the outlook is uncertain. House Speaker John Boehner says he has no plans to hold a vote on the Senate bill.
Many in the GOP-controlled House oppose the pathway to citizenship at the center of the bill. Rather, many prefer a piecemeal approach versus a sweeping bill like the one the Senate produced.
The House Judiciary Committee is working on a piece-by-piece effort, signing off Wednesday on legislation to establish a system requiring all employers within two years to check their workers' legal status.
In downtown Los Angeles Thursday morning, supporters gathered at a 24-hour vigil calling on Congress to pass the bill.
Those participating in the downtown rally say while this bill would be a step forward, they're urging Congress to strengthen family unity and family reunification. The Coalition for Humane Immigrant Rights of Los Angeles (CHIRLA) is calling for an end to deportations, clearing of decades-long family visa backlogs, inclusion of lesbian, gay, bixesual and transgender families and a stop to workplace raids and abuses.
The Associated Press contributed to this report.