The forum, held at Warren's Saddleback Church in California, brought the two candidates to the same stage for the first time since they secured the nomination from their parties.
First up for questions from Warren was Democratic candidate Obama, who reaffirmed that marriage was a "sacred union" between a man and a woman but also defended his support for civil unions between same-sex couples.
"I think my faith is strong enough and my marriage is strong enough that I can afford those civil rights to others even if I have a different perspective," Obama said.
Republican nominee McCain stressed his support for "the unique status of marriage between a man and a woman", saying he opposed the legalisation of same-sex marriages in some states.
"That doesn't mean people can't enter into legal agreements. That doesn't mean that they don't have the right of all citizens," he added.
The two candidates took questions from Warren for one hour each, but were not allowed to listen in on each other's interview during the forum, which was televised across the US and broadcast worldwide via the internet.
During the interviews, Obama was more open about his personal faith than Episcopalian-turned-Baptist McCain, whose reticence on the subject has jeopardised his support among Christian voters looking for a candidate who is prepared to speak up for Christian values in the face of encroaching secularism and liberalism.
When asked by Warren what being Christian meant to him, Obama quoted Micah's command to "walk humbly with your God".
"I know that I don't walk alone, and I know that if I can get myself out of the way, that I can maybe carry out in some small way what He intends," he said.
He said that one of America's greatest moral failures lay in not doing enough to support people on the margins.
"We still don't abide by that basic precept of Matthew that whatever you do for the least of my brothers, you do for me," Obama told the mega-church pastor.
Answering the same question later on, McCain said that America's greatest moral failure lay in citizens failing to "devote ourselves to causes greater than our self-interests".
When Warren asked McCain what it meant to him to be a Christian, the Republican candidate answered, "It means I'm saved and forgiven."
The two candidates differed most notably on the abortion issue.
Obama stressed his commitment to choice and upholding the Roe vs Wade Supreme Court ruling in favour of abortion.
"I think that whether you are looking at it from a theological perspective or a scientific perspective, answering that question with specificity, you know, is above my pay grade."
He added, however, that he would remain committed to cutting the number of late-term abortions and unwanted pregnancies.
McCain, meanwhile, won applause from the packed church when he said: "I will be a pro-life president and this presidency will have pro-life policies. That is my commitment to you."
Obama and McCain met briefly on stage, shaking hands and sharing a quick hug.
Christians are a crucial voting bloc in the US, making up around 25 per cent of the voting population.
