The trip -- with stops in Morocco and Spain -- will highlight the first lady's "Let Girls Learn" initiative aimed at helping adolescent girls get a quality education.
"This trip will allow the first lady to reach directly to publics of three important U.S. partners and talk about an issue that is important to all of us: The education of girls, and the empowerment of women and girls more broadly," Ben Rhodes, deputy national security adviser, said Friday.
Obama tweeted Monday about meeting Liberian girls who were not in school.
Upon the Obamas' arrival in Liberia, the first lady's office announced that USAID is dedicating up to $27 million to educational programs in Liberia and expanding the "Let Girls Learn" Peace Corps program in Liberia with new trainees and volunteers working primarily on education.
Following the Ebola crisis in Liberia, the rate of girls dropping out of school has sharply risen after schools closed and students were forced to stay home.
On Monday, the first lady began her trip meeting with Liberian President Ellen Johnson Sirleaf, the first elected female head of state in Africa and an outspoken advocate for education.
The first lady's official Snapchat account posted a photo of Obama meeting with Sirleaf. The Snapchat account was launched specifically for the trip so students in the United States follow the visit and to highlight the plight of the 62 million girls around the world who are not in school, according to the White House.
In addition to her daughters, the first lady will also be joined at several stops by actresses and education advocates Meryl Streep and Frida Pinto.
Pinto will moderate a discussion Monday between Obama and adolescent girls who have faced obstacles obtaining an education in Liberia and looking at the impact of the Ebola outbreak.
On Tuesday, both Pinto and Streep will take part in a panel discussion with the first lady moderated by CNN's Isha Sesay in Marrakesh.
On Wednesday, the first lady and her daughters will travel to Madrid, where Obama will deliver remarks on girls' education.
President Barack Obama is set to visit Spain for the first time next week as president. He has not visited Liberia during his White House tenure.
CNN Films is filming a documentary during Obama's trip, featuring the stories of girls who have overcome barriers going to school in Liberia and Morocco.