The high-speed line, linking London with cities in the Midlands and north of England, is planned to run through Andy Burnham's Leigh constituency, where he said an "absolutely massive" depot would be built on what is currently green space, but the Greater Manchester suburb will not have a station.
Mr Burnham is one of four prominent Labour frontbenchers who have raised concerns about the plan in formal submissions to the consultation on the new route. In his submission, he said that while he could "see a case for" the HS2 plans, he was concerned about their impact on his constituency.
"They deliver maximum disruption and minimal benefit to an area which has among the poorest access to rail transport of any in the country," he said.
Speaking to the New Statesman, Mr Burnham made clear he is ready to consider rebelling on the issue against leader Ed Miliband, who has voiced Labour's support for the scheme.
"It comes right through my constituency and it's made me look at it in a very hard-headed way," Mr Burnham said, adding: "I'm talking as the MP for Leigh."