Goals from AC Milan's Carlos Bacca and Real Madrid star James Rodriguez secured a 2-1 win for Colombia over Paraguay in front of a vocal crowd at the Pasadena Rose Bowl in California.
Victor Ayala gave Paraguay hope after pulling a goal back on 71 minutes but Colombia held on for three points which means they are assured of a top two finish in Group A and a place in the last eight.
Colombia need only to draw against Costa Rica on Saturday to assure themselves of first place, leaving them a potentially easier quarter-final against the runner-up from Group B, which contains Brazil, Ecuador, Haiti and Peru.
In Tuesday's other game, US striker Clint Dempsey scored his 50th international goal as the host nation bounced back from their 2-0 loss to Colombia on Friday with a convincing rout of Costa Rica.
Dempsey opened the scoring from the penalty spot after nine minutes before Jermaine Jones and Bobby Wood struck just before half-time to effectively settle the contest.
Substitute Graham Zusi added a fourth goal three minutes from time, which could prove crucial if goal difference comes into play.
The win came as a welcome relief for US coach Jurgen Klinsmann, whose tenure has faced mounting criticism over the past 18 months after a series of disappointing performances in competitive matches.
United States Soccer Federation chief Sunil Gulati had fueled fresh speculation about Klinsmann's position only hours before kickoff, telling journalists: "No one has iron-clad job security.