The U.S. extended its unbeaten streak to 33 matches, and its undefeated streak on home soil to 49.
It was the first home game for the Americans since the SheBelieves Cup last March. Colombia did not play a match last year.
Megan Rapinoe also started after taking much of last year off because of concern over COVID-19.
Rapinoe served up a perfectly placed cross to Sam Mewis in front of the goal in the fourth minute. Sam Mewis, who plays for Manchester City in England's FA Women's Super League, scored again in the 33rd minute. She converted a penalty kick early in the second half to complete her hat trick.
Kristie Mewis, who came on as a substitute in the second half, scored in the 86th minute. It was her third international goal.
"I'm just so proud of Kristie. I think it's so cool to watch her success here and to have her here,'' said Sam Mewis, the reigning U.S. Soccer Player of the Year. "I feel so lucky that we both get to be here and it's just been so much fun.
"It's the first game of 2021, we wanted to start the year off on the right foot. We definitely had been preparing hard for this game so it feels good to come away with a win as a team.
"Then to have some individual success and then to see Kristie score a goal as well, it was just so much fun and I really am just so proud of her."
Catarina Macario also came off the bench in the second half, making her first appearance for the national team. Macario, who was born in Brazil, became a U.S. citizen last fall and recently received approval from FIFA to play for the Americans.
Macario decided to forgo her senior season at Stanford and sign with French powerhouse Lyon.
Colombia were without three players -- midfielders Daniela Montoya, Diana Carolina Ospina and defender Carolina Arias -- who are in isolation because of COVID-19 tracing protocols. A fourth player, midfielder Ana Gabriela Huertas, had inconclusive test results and was ruled out of the match.
U.S. coach Vlatko Andonovski announced before the game that defender Becky Sauerbrunn would take over as team captain. In recent years, the captain's armband was passed among a group of veterans, including Rapinoe and Lloyd. Andonovski, who replaced Jill Ellis after she stepped down following the 2019 World Cup victory, is 12-0-0 as the U.S coach.
"I thought we did a good job but at the same time I want to give credit to the Colombian players for doing a great job in the one-vs-one duels," Andonovski said. "When we were putting pressures on individual duels I thought that was the only area we could have done a little bit better."
The teams are set to play at Exploria Stadium again on Friday.