President Barack Obama has called on the US Congress to pass immigration reform by the end of summer.
On Tuesday afternoon, the Senate voted to begin debate on a bill to overhall immigration by 82 votes to 15.
Senators will now consider a series of amendments with an aim to take a final vote before the 4 July recess.
Aside from a path to citizenship for immigrants who came to the US illegally, the legislation also creates new or expanded visa programmes for high-skilled and agricultural workers.
The BBC reports an estimated 11 million people live in the United States illegally.
The bill enjoys bipartisan support. But several Republican senators have called for significant changes, including stricter border control measures.
The legislation includes $US6 billion in border control funds.
The BBC reports the growing political clout of Hispanic voters has encouraged many in Congress to take up immigration reform.
Before Tuesday Mr Obama largely stayed out of the public negotiations over the bill. He received an overwhelming majority of the Hispanic vote in November's election.
"There's no reason Congress can't get this done by the end of the summer," he said.