McCain died at 4:28 p.m. MST, his office announced. His wife and other family members were with him.
Destined to be remembered among the political giants of Arizona history, the six-term U.S. senator disclosed in July 2017 that he had been diagnosed with a deadly form of brain cancer called glioblastoma.
Meghan McCain, his TV commentator daughter, wrote Saturday on Twitter: "I love you forever - my beloved father."
McCain was a two-time presidential candidate, losing the GOP nomination in 2000 to then-Texas Gov. George W. Bush and the general election in 2008 to then-Sen. Barack Obama.