The South Americans did not take long to strike with Cristian Zapata delivering the first goal in the eighth minute, the defender seizing on a corner kick from the left and volleying the ball into the back of the net.
James Rodriguez scored the second from a penalty in the 42nd minute after DeAndre Yedlin had been penalised for handball, a call the Americans hotly contested.
"The hand ball was not a hand ball," defender Geoff Cameron told reporters. "We’re disappointed, obviously. But I thought we were the better team."
Rodriguez, the Real Madrid playmaker, made no mistake with the spot kick and the two-goal cushion proved enough to give Colombia the early leg up in Group A, which also includes Costa Rica and Paraguay.
The United States, hosting the tournament for the first time and looking for some consistency after a difficult year, showed fight late in the second half but were unable to finish what chances they created.
Still, they tried to put a positive spin on their efforts and said they were happy with how they successfully controlled possession against the 2014 World Cup quarter-finalists.
"We were okay with the team performance. Against a quality team, if you don’t score a goal to get back in the game and equalise it's tough," said U.S. coach Jurgen Klinsmann.
"But overall we were totally even and we didn’t give them anything."
Clint Dempsey produced the best scoring opportunity for the Americans with a 63rd minute free kick that Colombia goalkeeper David Ospina saved at full stretch.
Ultimately, though, the end result was the hosts' sixth straight defeat in Copa America matches.
It was in line with U.S. form over the last year. The Americans finished just fourth in last year’s Gold Cup and suffered a deflating defeat to Guatemala in March that led to calls for German Klinsmann to be dismissed.
The U.S. next face Costa Rica in Chicago on Tuesday, while Colombia remain in California to take on Paraguay at the Rose Bowl in Pasadena later that same evening.
(Writing by Jahmal Corner, editing by Nick Mulvenney)
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