In 2000, promising the country “straight talk” and extensive government reform, McCain ran for the Republican presidential nomination, competing against Texas Gov. George W. Bush. Bush prevailed after a strenuous fight, including an especially brutal effort by the Bush campaign in the South Carolina primary. McCain eventually recovered from his devastating defeat, campaigned hard for Bush’s reelection in 2004, gave unswerving support to the Iraq War, and, after initially opposing Bush’s tax cuts, voted against their repeal.

In 2007 McCain announced that he would once again seek the Republican presidential nomination. Despite his rapprochement with the Bush family, his campaign seemed to be in serious trouble as the election year approached, lacking money and a clear political base. But after a decisive victory in New Hampshire and a strong showing on Super Tuesday, McCain took a commanding lead, and he secured the nomination with his victories on March 4, 2008. In late August he chose Sarah Palin, the governor of Alaska, as his vice presidential running mate.

McCain faced a challenging political climate in the general election. After 40 years of conservative dominance, the public seemed eager to start anew. By aligning himself with President Bush, McCain gained powerful political resources, but it remained to be seen how much Bush’s hard-core supporters, especially among religious conservatives, would rally to McCain’s cause, despite his efforts to court them. By sidling up to Bush, McCain also contradicted his reputation for independence, made himself look inconsistent on key issues (including taxes), and identified himself with a president who in his second term earned the longest sustained period of public disapproval ever. McCain remained far more popular with the public than his party did, but, as he took on Democrat Barack Obama, he faced the humbling irony that, having been defeated by George W. Bush in 2000, he might find himself defeated by the legacy of Bush’s presidency in 2008.

Indeed, in the event, McCain lost to Obama. Trailing in the initial opinion polls, McCain appeared to rebound following the Republican national convention in early September. His choice of Palin, a social conservative, as his running mate—the first female ever nominated to a Republican national ticket—initially stirred great excitement, particularly within the party’s social conservative base. But Palin soon received harsh criticism from many commentators, including conservatives, who claimed her lack of experience raised doubts about McCain’s judgment. The outcome became almost inevitable when, later in September, the failure of some major investment houses and banks signaled the start of what became widely described as the worst financial crisis since the Great Depression. McCain strangely suspended his campaign, just prior to the first scheduled presidential debate, in order to work on a congressional bailout of the financial industry. He then just as suddenly decided to participate in the debate, which made him look erratic—and when House Republicans rejected the proposed bailout bill, he looked ineffectual as well. Obama wound up winning nearly 53 percent of the popular vote—a decisive margin, but no landslide—yet also captured not only all of those states that had gone for John Kerry in 2004 but also a number of historically Republican states won by Bush in the 2000 and 2004 elections, including Colorado, Florida, Nevada, North Carolina, Ohio, Indiana, and Virginia.

Later career

Humbled but determined that his political legacy would not be as a failed presidential candidate, McCain returned to the Senate, where he continued to play a prominent role. In 2013, as part of the “gang of eight” group of Republican and Democratic senators, McCain pursued a bipartisan solution to immigration reform that included a “path to citizenship” for undocumented immigrants. In August 2013, at the request of President Obama, McCain and South Carolina Sen. Lindsey Graham, McCain’s longtime colleague and friend, traveled to Egypt, where they held separate meetings with that country’s new interim leaders and with the Muslim Brotherhood. After Republicans gained control of the Senate in the 2014 election, McCain became the chairman of the powerful Armed Services Committee.

In 2016 McCain faced and ultimately fended off a primary challenge from former state senator Kelli Ward, whose adamant opposition to amnesty for illegal immigrants and whose calls to secure the border differed starkly from McCain’s tolerant stance but were in keeping with the strident approach taken by Donald Trump as a candidate for the Republican presidential nomination and as the party’s standard-bearer in the general election. Initially McCain provided consistent, if tepid, support for Trump’s candidacy, despite Trump’s criticism of what he characterized as McCain’s failure to support veterans and even after Trump controversially maligned McCain’s military record, saying that he liked “people who weren’t captured.” In October 2016 McCain withdrew his endorsement of Trump after a hot-mic video from an infotainment television program in 2005 surfaced in which Trump boasted to a reporter about sexual exploits that were grounded in predatory behaviour.

After Trump won the presidency, McCain was among a small group of Republicans who were critical of the new chief executive’s warm overtures to Russia and its president, Vladimir Putin, in the face of the consensus within the U.S. intelligence establishment that the Russian government had meddled in the 2016 U.S. presidential election. McCain joined Democrats in calling for the creation of a special committee to investigate the Russian intervention in the election and the possible collusion by the Trump campaign in that effort.

In mid-July 2017, following surgery to remove a blood clot over McCain’s left eye, it was announced that McCain was suffering from glioblastoma, a common but extremely malignant brain tumour. Joining other former presidents and a chorus of McCain’s Senate colleagues in offering messages of support for McCain, Obama tweeted, “Cancer doesn’t know what it’s up against. Give it hell, John.”

On July 25 McCain returned to the Senate to cast a pivotal vote to open debate on the Republican effort to repeal the Patient Protection and Affordable Care ACT (PPACA, “Obamacare”). Speaking on the floor after casting his vote, McCain called for the Senate to return to “regular order,” transcend partisanship, and work toward compromise. In the wee hours of the morning of July 28, joining the Democrats in opposition, McCain and fellow Republican senators Susan Collins (Maine) and Lisa Murkowski (Alaska) cast the deciding votes to block (51–49) their party’s attempt to repeal the PPACA. In December, on the other hand, McCain demonstrated his fidelity to his party’s goals by lending his influential support to help secure passage of the sweeping tax-cutting legislation that had been at the top of Republican wish lists for years.

When McCain succumbed to his illness in August 2018, his passing was mourned and his character and patriotism were praised across the political spectrum. In the farewell message that he left to be shared after his death, McCain wrote (in part):

We weaken our greatness when we confuse our patriotism with tribal rivalries that have sown resentment and hatred and violence in all the corners of the globe. We weaken it when we hide behind walls rather than tear them down, when we doubt the power of our ideals, rather than trust them to be the great force for change they have always been.…Do not despair of our present difficulties but believe always in the promise and greatness of America, because nothing is inevitable here. Americans never quit. We never surrender. We never hide from history. We make history.

McCain coauthored several books, including Faith of My Fathers (1999), Worth the Fighting For: A Memoir (2002), Why Courage Matters: The Way to a Braver Life (2004), Hard Call: Great Decisions and the Extraordinary People Who Made Them (2007), Thirteen Soldiers: A Personal History of Americans at War (2014), and The Restless Wave: Good Times, Just Causes, Great Fights, and Other Appreciations (2018). McCain was posthumously awarded the Presidential Medal of Freedom in 2022.