McCain had been away from the Senate floor since last December, remaining at his ranch home for treatment of glioblastoma - the same form of brain cancer that took the life of another Senate giant, Democrat Ted Kennedy, in 2009.
But on Friday his family announced he had chose to discontinue that treatment.
But in his address to the US Studies Centre previous year, Senator McCain did not shy away from conceding that Mr Trump was "unsettling" American allies, or that there is a debate underway in the United States about its role in the world, its resolution uncertain.
"Karen and I send our deepest condolences to Cindy and the entire McCain family on the passing of Senator John McCain", the vice president said.
Following the announcement of his death on Saturday evening, United States president Donald Trump said his "deepest sympathies" went to Mr McCain's family.
Trump also posted about McCain's death on his Instagram page - in a fashion that drew near-immediate condemnation.
McCain clinched the Republican presidential nomination in 2008 to face Democrat Barack Obama.
However, he was unable to do so as John McCaincast the deciding vote against the repeal. Barak added that McCain was "a huge friend to Israel, especially regarding its security".
"Why don't we try the old way of legislating in the Senate, the way our rules and customs encourage us to act?"
"Sen. Chris Van Hollen:John McCain's passion and determination were unsurpassed in the Senate, and his moral compass was unfailing".
McCain spent more than three decades in Congress and ran for president twice. The family announced on Friday that McCain had made a decision to discontinue medical treatment.
Over the course of his career he rallied against pork-barrel spending and went against his own party's president, George W. Bush, on strategy for the Iraq war.
McCain long cultivated the image of a Republican maverick, defying his party on issues ranging from campaign finance reform to immigration.
The pair would lose to former President Barack Obama in a landslide.
His contentious choice for a running mate, Sarah Palin, the governor of Alaska at the time, was also believed to have contributed to the loss, and is still seen by some as a tarnish on his reputation.
Some speculate that Cindy McCain could join their ranks.
"John McCain's life is proof that some truths are timeless".
McCain then headed off to U.S. Naval Academy in Annapolis, MD, graduating in 1958 near the bottom of his class, ranking 894 out of 899.
In a speech to midshipmen at his alma mater in October 2017, McCain joked about his abysmal academic performance.
On his 23rd combat mission over North Vietnam, McCain's plane was shot down with a surface-to-air missile.
He broke both arms and a leg in the crash.
His captors offered him early release after learning his father was a notable naval officer. But in a fresh sign of hostility, Trump, who once said he didn't consider McCain a war hero because he was captured, didn't even mention the Arizona senator's name. He was severely injured and taken prisoner.
"I fell in love with my country when I was a prisoner in someone else's", he said in accepting the Republican presidential nomination. In 1986, he was elected to the Senate to succeed Barry Goldwater, the failed Republican presidential hopeful.
According to the New York Times, McCain has made clear to the White House he doesn't want Trump to attend his funeral, and would instead prefer Vice President Mike Pence at a service.
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