Tony Nicklinson, 58, from Melksham, in Wiltshire, was left suffering from locked-in syndrome after a stroke in 2005. He is paralysed below the neck and communicates by blinking.
He wanted assurance that doctors who helped to end his life would not face a murder charge.
The court also decided against the case of another locked-in sufferer, named only as Martin, who had sought permission for volunteers to assist him in getting to the Dignitas clinic in Switzerland.
Lord Justice Toulson said: "A decision to allow their claims would have consequences far beyond the present cases.
"To do as Tony wants, the court would be making a major change in the law.
"It is not for the court to decide whether the law about assisted dying should be changed and, if so, what safeguards should be put in place.
"Under our system of government these are matters for Parliament to decide."
Mr Nicklinson and his wife said they would challenge the High Court's decision.
Dr Andrew Fergusson, spokesman for campaign group Care Not Killing, welcomed the judgement.
"It confirms the simple truth that the current law exists to protect those without a voice: the disabled, terminally ill and elderly, who might otherwise feel pressured into ending their lives," he said.
“The ruling confirms the view that even in a free democratic society there are limits to choice. Every law limits choice and stops some people doing what they might desperately wish to do, but this is necessary in order to protect others, especially the most vulnerable in our society.
“Hopefully the decision to reject both cases will now draw a line once and for all under legal debate and allow decision makers and society to focus attention on how we care for the terminally ill and severely disabled.”