In a criticism of his own party, he said he would "fight to restore the pride and principles" of the party, damaged after some Republicans gave in to "the temptations of corruption".
"We're going to recover the people's trust by standing up again for the values Americans admire," he said. "The party of Lincoln, Roosevelt and Reagan is going to get back to basics."
Mr McCain then turned to attacking the Democrats over taxes and spending, saying they would seek to raise taxes whereas he would keep them low and cut them where possible.
Going into some policy specifics, he pledged create new jobs, improve education and to reduce a "dangerous dependence on foreign oil" by producing more energy at home, including by drilling new offshore oil wells.
Mr McCain promised to take a bipartisan approach to resolving the nation's problems, saying: "Again and again, I've worked with members of both parties to fix problems that need to be fixed.
"That's how I will govern as president. I will reach out my hand to anyone to help me get this country moving again.
"I have that record and the scars to prove it. Barack Obama does not."
After speaking of the five years he spent as a prisoner of war in Vietnam and how that experience had inspired his love of his country, he called on his fellow Americans to fight with him to make it a better one.
"Stand up, stand up, stand up and fight. Nothing is inevitable here. We're Americans and we never give up. We never quit. We never hide from history. We make history."
The almost hour-long speech, which ended in the traditional shower of confetti and red, white and blue balloons, brought to a close the party's four-day event.
'Tested and true'
The BBC's Adam Brookes in St Paul says Mr McCain's speech was measured and entirely lacking in the sarcasm and vitriol which have been levelled at Mr Obama over the past couple of nights.
He said he hated war and would use all America's tools - diplomatic, military and economic - to build what he called a stable and enduring peace, as well as shaking up Washington and including Democrats and independents in a McCain administration.
Mrs McCain praised her husband as a great father and devoted American
It was all a rather different tone to the Republican politics of the past eight years, and to many of the other speakers at this Republican convention, our correspondent says.
There was very little of President George W Bush in this speech, our correspondent adds, as Mr McCain tries to show that he is his own man and can signify a break with the Bush years.
Mr McCain's wife, Cindy, in her speech praised her husband's family values, strength of character, war service and leadership.
"If Americans want straight talk and the plain truth, they should take a good close look at John McCain... a man tested and true, who's never wavered in his devotion to our country," she said, after arriving on stage flanked by their seven children.
Her speech followed the convention's formal nomination of Mrs Palin - the Republican Party's first female vice-presidential candidate.
Mrs Palin becomes only the second woman, the first being Democrat Geraldine Ferraro in 1984, to run for the US vice-presidency.
'Integrity and courage'
Speaking ahead of Mr McCain's address, senior Republicans praised his courage and leadership.
I have to say, from my vantage point next to the DC delegation, my overall impression was that the audience in the hall were disappointed
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