Christian leaders have warned that "cutbacks and failures" in the system were forcing thousands of people to use food banks.
But appeal judges have ruled that two of the Government's most controversial measures - the so-called "bedroom tax" and the benefit cap - were not unlawful.
Lord Dyson, Master of the Rolls, rejected a two-pronged legal attack and said the court could only intervene if the measures "were manifestly without reasonable foundation". He ruled that that test was not satisfied.
Campaigners vowed to fight on, saying the cuts were having a "devastating" impact on vulnerable people.
The Department for Work and Pensions was a defendant in both legal actions.
A spokesman said of its bedroom policy: "Reform of housing benefit in the social sector is essential to ensure the long-term sustainability of the benefit. But we have ensured extra discretionary housing support is available for vulnerable people."
Ugo Hayter, from law firm Leigh Day, representing two of the disabled appellants, said an appeal to the Supreme Court was under consideration, adding: "We are extremely disappointed by this judgment and we are baffled by the findings of the Court of Appeal."
Richard Kramer, deputy chief executive of Sense, the national deafblind charity, said: "We know from our experiences of supporting deafblind people that the bedroom tax has adversely affected disabled people."