Jobs at Sellafield depend on the new plant
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The groups, Friends of the Earth (FoE) and Greenpeace, are seeking a judicial review of the decision in the High Court in London. The hearing, starting on Thursday, is expected to last two days.
Judgement is likely to be reserved for a week or so. However, this is but one of several cases challenging the plant.
The Irish Republic has also started legal action against the decision to give the go-ahead for the new Mox plant.
It claims the decision to allow the fuel production centre to be built on the Cumbrian coast broke international laws on sea pollution.
On 9 November, it is to ask the International Tribunal for the Law of the Sea to order an immediate suspension of the plant's authorisation.
Norway is also reported to be considering legal action to stop the Mox plant opening.
FoE and Greenpeace rely on two arguments in claiming that the government acted unlawfully in allowing the plant to start. They say:
Reduced stockpile
They cite a statement by the Environment Agency, which said: "It would be a relatively straightforward matter to undertake chemical separation of plutonium from Mox fuel.
"It is debatable how easy it would then be to assemble the plutonium into a crude nuclear device actually capable of exploding. A terrorist group would arguably be able to exercise considerable power by merely threatening to explode such a weapon."
The two groups are also concerned that fuel exported from the Mox plant by sea or air could be damaged in accidents or intercepted by terrorists.
Mox is a blend of plutonium and uranium that has been extracted from spent fuel rods already "burnt" in reactors.
The nuclear industry believes that such recycling could help reduce the world's growing stockpile of toxic plutonium.
Consultants say the plant's operation will be worth £150m to the UK over its lifetime. Local unions have welcomed the government's decision, which is expected to lead to up to 400 new jobs.