Liberal Democrat MP Lembit Opik, who became president of the charity in 2006 after his father died from motor neurone disease, last year called on Tony Blair to increase government funding for research into the disease.
Opik also said the association was starting a £15m campaign to fund its own research. His comments persuaded an unnamed relative of Lady Edith Wolfson, who died of the disease in 1981, to pledge the sum, which is more than a tenth of the association's £8.9m income.
The gift will be used to set up Lady Edith Wolfson Clinical Research Fellowships.
Jhumar Johnson, treasurer of the Institute of Fundraising's major donor special interest group, said an unsolicited gift of this size would make any fundraiser's year.
"Given how long it takes to raise funds this way, this is a godsend," she said.