U.S. Senator John McCain, a six-term Republican senator from Arizona and former prisoner of war during the Vietnam conflict, has died of brain cancer at age 81.

"Senator John Sidney McCain III died at 4:28 p.m. on August 25, 2018. With the senator when he passed were his wife Cindy and their family," his office said in a statement from the senator's home state.

"At his death, he had served the United States of America faithfully for 60 years," the statement added.

"My heart is broken. I am so lucky to have lived the adventure of loving this incredible man for 38 years," his wife, Cindy, wrote on Twitter. "He passed the way he lived, on his own terms, surrounded by the people he loved, in the place he loved best."

After his illness became public, McCain received high praise from Republicans and Democrats alike, although U.S. President Donald Trump continued to verbally attack the senator who had often criticized the president of his own party.

After his death, however, Trump issued a Twitter statement saying, “My deepest sympathies and respect go out to the family of Senator John McCain. Our hearts and prayers are with you.”

Former President Barack Obama, who defeated McCain in the 2008 presidential election, said that "we are all in his debt."

"John McCain and I were members of different generations, came from completely different backgrounds, and competed at the highest level of politics," Obama said in a statement.

"But we shared, for all our differences, a fidelity to something higher -- the ideals for which generations of Americans and immigrants alike have fought, marched, and sacrificed."

McCain was often praised for his willingness to cooperate with Democrats on difficult issues.

The secretary of defense, Jim Mattis, hailed the man many considered a war hero, saying, “We have lost a man who steadfastly represented the best ideals of our country."

With his time running out, in recent months McCain had surrounded himself with family and friends at his Arizona ranch and published what would turn out to be his last book, The Restless Wave: Good Times, Just Causes, Great Fights, and other Appreciations.

McCain, a longtime chairman of the Senate's Armed Services Committee, was considered an expert on defense and foreign policy issues.

Despite being in the same political party, McCain often took issue with Trump’s policies, especially in regard to what was perceived as the president’s friendly statements about Russia and President Vladimir Putin.

McCain last month said that "Putin is not America's friend, nor merely a competitor. Putin is America's enemy — not because we wish it so, but because he has chosen to be."

McCain in 2017 was also the deciding vote in the Senate to reject Trump’s effort to overturn Obama’s signature health-care plan, angering Trump.

He was the son and grandson of U.S. Navy admirals and endured almost six years of torture and captivity in a North Vietnam prison after his plane was shot down in 1967 at age 31 on a mission during the long U.S. war.

After learning of his family connections, his North Vietnamese captors offered him early release in what would have been a propaganda ploy. McCain refused to leave and said those captured before him should be the first to leave.

McCain returned home five-and-a-half years later on crutches and never regained full mobility in his arms and leg.