Wes Streeting will vote against assisted dying over concerns end of life care is not good enough for people to make an informed choice.
As first reported by The Times, the health secretary told backbench MPs of his position during a regular meeting on Monday, blaming the state of the NHS.
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It makes him the highest-profile MP to come out against legalising euthanasia, and the second cabinet minister to do so.
Justice Secretary Shabana Mahmood has also spoken against it, saying that as a Muslim she has an "unshakeable belief in the sanctity and the value of human life".
The proposal is being championed by Labour's Kim Leadbeater, who wants to give terminally ill people the choice to end their lives.
Her Terminally Ill Adults (End of Life) Bill was formally introduced to parliament last week and is due to be debated and possibly voted on for the first time next month.
MPs will be given a free vote, meaning they can decide with their conscience rather than along party lines.
However, cabinet secretary Simon Case has written to ministers to say that, while they "need not resile from previously stated views" on assisted dying when directly asked, they "should exercise discretion and should not take part in the public debate".
Mr Streeting backed assisted dying last time it was debated by parliament in 2015, but he has recently expressed doubts about changing the law.
In comments reported by The Sun at the weekend, he said: "The challenge is, I do not think palliative care, end-of-life care, in this country is good enough to give people a real choice.
"I worry about coercion and the risk that the right to die feels like a duty to die on the part of, particularly, older people."
The health secretary's comments are said to have weighed heavily with some MPs who are still on the fence.
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As well as the issue of end of life care, critics like the Archbishop of Canterbury have also expressed concern that legalising assisted dying could lead to a "slippery slope" of widening criteria.
Ms Leadbeater has rejected that argument, insisting her bill would only apply to terminally ill adults and with safeguards in place.
She has told Sky News the legislation is about giving terminally ill people a choice, saying if they want to end their lives their only options at the moment are "suicide, suffering, or Switzerland".
The precise detail of the proposed legislation - setting out the circumstances which could lead someone to be eligible - is not expected to be published until closer to the 29 November debate.
If the bill passes the first stage in the Commons, it will go to committee stage where MPs can table amendments, before facing further scrutiny and votes in both the House of Commons and the House of Lords.
That means any change in the law would not be agreed until next year at the earliest.
If MPs vote against it at the first hurdle, as they did last time changes to the law were considered, that would prevent it going any further.
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