The visit is also viewed as a bid to contrast McCain's foreign policy experience with that of Barack Obama, his Democrat rival.
Al Jazeera's Monica Villamizar in Cartagena says McCain wants to show that Republican policies towards Colombia are working, with the country the US's strongest strategic ally in a region where many nations are turning to more left-wing leaders.
Free trade row
The US congress has blocked a free trade deal with Colombia that was backed by the Bush administration, with Democrats citing concerns over the killing of trade unionists by paramilitary groups.
McCain, however, has made it clear he is committed to the deal, which is opposed by Obama.
"He doesn't support the Colombian Free Trade Agreement. I think it would ... have very serious consequences if we rebuked our closest ally," McCain said before leaving for Colombia.
The Arizona senator also defended Uribe for attacking the Revolutionary Armed Forces of Colombia (Farc), Colombia's largest armed rebel group.
"We all are advocates of human rights, and the nation of Colombia is going though one of the bloodiest civil wars that we've ever seen in our hemisphere," he said.
"Thanks to the leadership of President Uribe and the support of the people of Colombia, they've made significant progress against Farc."
Obama, an Illinois senator, has also called for the North American Free Trade Agreement (Nafta), which includes Mexico the US and Canada, to be renegotiated to improve environmental and labour provisions.
He has threatened to pull out of the pact if necessary if the changes are not made.
McCain has criticised his opponent's position and used a trip to Canada last month to highlight his own support of Nafta.
McCain's stance on illegal immigration, a fiercely contested issue in the US, will come under the spotlight in Mexico.
Last year, his support for a comprehensive immigration reform bill in Congress was a contributing factor to a slump which almost doomed his campaign.
Since then, McCain has said the US needs to strengthen border controls before tackling the problem of millions of illegal immigrants.
However, the issue is key for the millions of Latino voters in the US who could prove key to victory in November's poll.