The summit would have been Trump's first trip to the region.
In a brief statement, Sarah Huckabee Sanders, the White House press secretary, said the President would stay in the United States and oversee America's response to a suspected and deadly chemical attack in Syria, "and to monitor developments around the world".
Trump had been due to attend the Summit of the Americas in Lima and travel to Colombia. The White House says canceling the trip allows Trump to focus on the latest crisis in Syria.
"As you work for change, the United States will stand up alongside you every step of the way".
Like Trump, Pence is expected to use the summit to push for a stronger response to what the US considers the rise of dictatorship in Venezuela. Whereas President Barack Obama had an average rating of 7 out of 10 after his first year in office, Trump ended his with less than half that rating.
Last week before Trump made a decision to skip the Summit, administration officials ruled out any chance of a one-on-one Trump-Castro meeting during the two-day conference.
During that trip, Pence met with the presidents of Argentina, Chile, Colombia and Panama to negotiate trade deals and discuss concerns about Venezuelan President Nicolas Maduro's regime, which has been described as increasingly dictatorial by the US and Colombia.
The meeting, which now is expected to be handled by Pence, also was expected to cover the construction of a wall on the U.S. -Mexico border.
Sen. Marco Rubio, (R., Fla.) on Tuesday during a Senate Foreign Relations subcommittee hearing highlighted the Summit as an opportunity for the administration to demonstrate its commitment to the region and to promote the restoration of democracy in Venezuela. He would not describe the USA response or say when it would come.
During the hearing, Rubio blamed the "puppet masters in Havana" for Venezuela's decision to "replace its democratic elected government with a dictatorship", by disbanding the elected National Assembly and reconvening another filled with Maduro supporters. Pence will travel to the summit in his place, but will not go to Colombia. Vice President Pence also hosted the Northern Triangle Conference on Prosperity and Security in Central America as well.