His family said he had "surpassed expectations for his survival" and made the choice to end his treatment.
Mr McCain, 81, was diagnosed with an aggressive brain tumour in July 2017 and had been undergoing medical treatment.
He left Washington in December, but has remained a vocal political figure.
His family said in a statement shared with US media: "Last year, Senator John McCain shared with Americans the news our family already knew: he had been diagnosed with an aggressive glioblastoma, and the prognosis was serious.
"In the year since, John has surpassed expectations for his survival. But the progress of disease and the inexorable advance of age render their verdict.
"With his usual strength of will, he has chosen to discontinue medical treatment."
The six-term senator and 2008 Republican presidential nominee was diagnosed after doctors discovered his tumour during surgery to remove a blood clot from above his left eye last July.
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