Under Secretary of State for Political Affairs Wendy Sherman arrived in the northern city of Cartagena, where the summit will host 34 leaders from the Americas, including United States President Barack Obama.
After visiting the summit venue, Sherman will travel to Bogota to meet Santos. She will then hold separate meetings with Foreign Minister Angela Holguin and Defense Minister Juan Carlos Pinzon.
In an official statement the State Department said the visit will include discussions of regional security, the fight against drugs, human rights and free trade.
Pinzon recently met Venezuelan counterpart General Henry Rangel, who is listed by the State Department as having links to the FARC and to drug trafficking, to discuss security along the Colombia-Venezuela border.
Sherman will also visit Brazil and Mexico on her trip.