Petro said he has been actively combating drug trafficking and called the US action a paradox.
"Fighting drug trafficking for decades and doing so effectively brings this measure upon me from the government of the society that we help so much to stop their cocaine consumption," he wrote on X.
"Quite a paradox, but not a step back and never on our knees," he added, saying he would file a legal appeal.
"My lawyer in my defense will be Dany Kovalik from the US," Petro said, Anadolu Agency reported.
The US Treasury Department also sanctioned Petro’s wife, one of his sons, and Interior Minister Armando Benedetti.
The sanctions came as Washington announced the deployment of an aircraft carrier and support ships to reinforce its Latin America fleet dedicated to “countering narco-terrorism.”
It is the first time a sitting Colombian president has been subjected to US sanctions.
US Secretary Scott Bessent claimed, “President Petro has allowed drug cartels to thrive and has refused to stop this activity.”
He added that US President Donald Trump “is taking strong action to protect” the country.