Jeremy Bamber and two other killers are to ask the European Court of Human Rights to rule on whole-life sentences.
The murderers say condemning them to die in prison amounts to "inhuman or degrading treatment", claiming all jail sentences should be regularly reviewed.
The Ministry of Justice defended the sentences. A source stressed that, if the inmates win, they would not secure their release, just periodic reviews.
Bamber was jailed for shooting five of his family dead in Essex in 1986.
He has always protested his innocence, claiming his schizophrenic sister shot the victims before turning the gun on herself in their remote farmhouse.
Also fighting the sentences are Peter Moore, convicted of murdering four gay men for his sexual gratification, and Douglas Vinter, who killed both his wife and a work colleague.
The trio's legal team say any sentence under which the offender's rehabilitation cannot lead to a review of release breaches articles three, five and seven of the European Convention on Human Rights.
An oral hearing is due in the autumn and a judgment is expected next year.
Justice Secretary Ken Clarke said: "The government will argue strongly that this application should be rejected.
"It goes without saying that the government will be fighting the case vigorously and defending the principle of the whole-life tariff."
He continued: "There will always be a small number of prisoners whose crimes are so appalling that judges rule that they should never become eligible for parole.
"Their decisions should be upheld."
A Ministry of Justice spokesman said his understanding was that if the prisoners were successful, the ruling would only apply to the UK, and not be Europe-wide.
'Tooth and nail'
Inmates serving similar sentences elsewhere in Europe would have to apply to the European court for a similar judgement to be made regarding their country, although the "outcome would be predictable", he said.
But he said the government would fight the case "tooth and nail".
In a separate case in 2008 the UK's Court of Appeal found whole-life sentences did not constitute cruel or inhuman treatment.
Currently whole life tariff prisoners stand virtually no chance of release as their offences are so serious.
Only the secretary of state can free them on compassionate grounds if the prisoner is terminally ill.
A total of 41 inmates are serving whole-life sentences in England and Wales.
Scottish judges do not have the power to hand out whole-life sentences.