His likely Democratic opponent in the November White House election, Barack Obama, firmly supports abortion rights.
Few other big issues cut so clearly across partisan lines in the United States, a point underscored by McCain and Obama's positions on it. And analysts say while both candidates must be careful they may need the issue to stir their party's bases.
In McCain's case that would be the evangelical Christians who account for one in four US adults and comprise a key base of support for the Republican Party - to such an extent that few analysts think he can win the presidency without them.
"Religious conservatives may not be wildly enthusiastic about McCain but they can point to his pro-life stance as reason to stay on board," said Matthew Wilson, a political scientist at Southern Methodist University in Dallas.
The Arizona senator's position on the issue distinguished him in the early stages of the Republican contest from former New York Mayor Rudy Giuliani, whose support for abortion rights dismayed conservative Christians and led to threats to form a third party if he had secured the nomination.
That signalled abortion was a line in the sand that this vital wing of the Republican Party would not cross and secured endorsements for McCain from leading conservative Christians such as Republican Kansas Senator Sam Brownback, whose own run for the nomination faltered.
Influential evangelicals like Focus on the Family's James Dobson, whose radio show reaches millions, have expressed their displeasure at McCain's past support for stem cell research and his failure to back a federal ban on gay marriage.
COMPARED TO SLAVERY
But nothing unites evangelicals like their opposition to abortion, which many compare to the anti-slavery movements of the past - a comparison that raises the moral stakes and suggests they will not back down on it.
Polls suggest the issue is becoming even more entrenched in conservative Christian culture.
An analysis of surveys from 2001 to 2007 by the Pew Forum on Religion & Public Life found that young white evangelicals between the ages of 18 and 29 were even more conservative on the issue than their elders.
It found 70 per cent said they were in favour of making it more difficult for a woman to get an abortion compared with 55 per cent of older white evangelicals and 39 per cent of young Americans overall.
