McCain also touted his own judgment for choosing Alaska Gov. Sarah Palin as his vice presidential running mate.
"I'm very proud to have introduced our next vice president to the country. But I can't wait until I introduce her to Washington. And let me offer an advance warning to the old, big-spending, do-nothing, me-first, country-second Washington crowd: Change is coming," McCain said.
McCain, whose campaign was bankrupt and believed dead only a year ago, also reminded Americans of his rough road to the nomination.
"In my life, no success has come without a good fight, and this nomination wasn't any different. That's a tribute to the candidates who opposed me and their supporters. They're leaders of great ability, who love our country and wished to lead it to better days. Their support is an honor I won't forget."
McCain, who clashed for years with the Bush administration for its handling of the war, offered praise for the current president and his father.
"I'm grateful to the president for leading us in those dark days following the worst attack on American soil in our history, and keeping us safe from another attack many thought was inevitable; and to the first lady, Laura Bush, a model of grace and kindness in public and in private. And I'm grateful to the 41st president and his bride of 63 years, and for their outstanding example of honorable service to our country," McCain said.
McCain, who has highlighted his experience in his bid for the White House, made national security a consistent theme of his address.
"We have dealt a serious blow to al Qaeda in recent years," he said, "But they are not defeated, and they'll strike us again if they can. Iran remains the chief state sponsor of terrorism and on the path to acquiring nuclear weapons. Russia's leaders, rich with oil wealth and corrupt with power, have rejected democratic ideals and the obligations of a responsible power."
McCain said, "We face many threats in this dangerous world, but I'm not afraid of them. I'm prepared for them. I know how the military works, what it can do, what it can do better, and what it should not do. I know how the world works. I know the good and the evil in it. I know how to work with leaders who share our dreams of a freer, safer and more prosperous world, and how to stand up to those who don't. I know how to secure the peace."
During Thursday's program, the Republican National Committee showed a video about the Sept. 11 terror attacks that included images of Osama bin Laden and the aftermath of the attacks, ending with old aerial footage of the World Trade Center towers still standing.
"It will never happen again," said the video's narrator over the images, as the crowd applauded, cheeing "USA! USA!"
Watching the program from the VIP seats was former Nixon administration national security adviser and secretary of state Henry Kissinger, who advised President Bush on the U.S.-led war on Iraq.
Anti-war protesters marched for a fourth night Thursday outside the Xcel Center as McCain delivered his acceptance speech.
Police arrested hundreds of people and fired tear gas and flash bangs at protesters trying to break up the crowds.