Sessions also takes aim at language in the bill swapping the existing E-verify system -- an Internet-based program used to check the legal status of potential employees -- with a new one that relies more strongly on photographic matches through passport and driver's license images, among other things.
Supporters insist the new version will be more effective, but Sessions says it's unproven and offers too much discretion to the Department of Homeland Security.
It "could be an improvement" but "it's dangerous the way (the provision) is written," the senator argued. "I'm wondering why they want to go around and create a new one."
Beyond disputes over specific provisions, Sessions makes what he characterizes as a broader moral argument against the proposal.
"I will not support citizenship for people who entered the country illegally," Sessions said. "There needs to be some difference between what we do for a person who enters the country legally and those who enter illegally.
"And there's no moral, no legal, no principled reason why this United States government should reward people who broke the law and entered the country illegally with every benefit that you give to somebody who comes lawfully."
The bill as currently written "just further incentivizes amnesties in the future," he argued, invoking one of the most bitterly contested terms of the debate.
While the Republican Party may be divided over immigration reform, analysts are not surprised by Sessions' role as leader of the Senate opposition.
"Given the politics of Alabama, it doesn't surprise me at all," said Richard Fording, chairman of the University of Alabama's political science department. "Politics here dictates you oppose whatever the president supports."
Fording noted Alabama's passage in 2011 of one of the strictest laws in the country designed to crack down on undocumented immigration. Among other things, the law requires police who make lawful traffic stops or arrests to try to determine the immigration status of anyone they suspect might be in the country illegally.
The law retains broad support in Alabama, Fording said, even crossing the state's traditional racial divide.
"There's nothing for Sessions to lose and maybe lots to gain" in opposing the "Gang of Eight" bill, Fording said.
As for political considerations on Capitol Hill, Sessions told CNN the "Gang of Eight" put its blueprint together using an "old fashioned, smoke-filled room strategy." As a result, he says, the bill was written by big labor and business interests.
"I've been around here a long time," he said. "I've never seen a more calculated, cold-blooded p.r. campaign managed to advance a piece of legislation than this one."
"The political consultants and pollsters and people (managing the bill) ... anticipated everything that was going to occur," he declared. "They planned on careful attacks to neutralize critics."
"But somebody needs to ask questions about this bill," he quickly added. "They don't get to write a bill in secret, and we all roll over and have it passed without examination."
And what about the argument that by opposing comprehensive immigration reform, Republicans risk permanently alienating America's rapidly growing Hispanic population? Sessions returns to his economic theme.
"I believe that, politically, at this point in time we should serve and listen to the concerns of the working Americans who are making $20,000 to $45,000 a year," Sessions said.
"That includes Hispanics, African-Americans, and Caucasians," he noted.
"One of the reasons their wages haven't gone up is because there's too much labor. And so, if we end the illegality with a good, principled immigration bill, (if) we allow a generous but responsible flow of immigrants in the future, and if we improve the lives of working Americans, then that's the way you win elections."