The nation -- which has never had a left-wing president -- has been Washington's closest ally in the region for decades. But the election of leftist former guerrilla Petro to the country's highest office could radically change that relationship.
In an interview with CNN last week, Petro said he intends to renegotiate Colombia's trade deals with the US.
He also plans to open dialogue around three main issues: protection for the Amazon rainforest; ending the war on drugs; and moving the Colombian economy away from extractive projects such as fossil fuels.
His future conversations with US President Joe Biden are likely to be tough, with the two leaders diametrically opposed on issues such as relations with Venezuela.
Although he tried to distance himself from the regime of Venezuelan strongman Nicolas Maduro on the campaign trail, Petro does support recognizing the authoritarian leader as the country's president, something the White House is firmly against.
But the two presidents might still find common ground in areas such as environmental protections and the energy transition.
And Petro has his own allies in Washington -- he told CNN that he speaks "often" with US Senator Bernie Sanders, and met in person earlier this year with the Progressive Caucus, a group of left-leaning US representatives.
Colombia's newest president has also spoken of a desire to create a new progressive alliance in South America.
This would likely involve Chilean president Gabriel Boric and Argentinian president Alberto Fernandez, rather than the three authoritarian countries of Cuba, Nicaragua and Venezuela.
Biden recently stoked opposition among some Latin American leaders by barring those three nations from the Summit of the Americas, a regional forum that took place in Los Angeles in early June. In solidarity, Mexican President Andres Manuel Lopez Obrador elected to skip the event entirely.
But Petro told CNN he would have attended anyway.
"Of course," he said. "I would have gone and told Biden it was wrong not to invite some countries, but I would never refuse an occasion for dialogue."