In a statement issued by her office, the first lady expressed empathy for affected families, saying the country should be governed "with a heart".
Democrats, though, say his zero tolerance policy of losing criminal charges against illegal immigrants has spurred the separations.
Despite that, presidential adviser Kellyanne Conway has rejected suggestions Mr Trump is using the children as leverage to force his opponents to enter negotiations on immigration and his long-promised border wall.
"Now as we watch with broken hearts, that's exactly what's happening", she said.
Additional reporting from Newsy affiliate CNN.
As reported by the Hill, the Trump's immigration policy is facing a backlash from both Democrats and Republicans, who call it inhuman to separate the minors from their families during immigration. Trump will make a rare trip up Pennsylvania Avenue to talk to the House GOP conference about immigration.
Lawmakers have traveled to South Texas where hundreds of children separated from their parents are being held to speak out against the zero-tolerance policy.
In under 24 hours, all five living first ladies spoke out against the Trump administration's lightning-rod "zero-tolerance" immigration policy of separating families at the border.
Trump blamed Democrats for not fixing the law, despite the GOP being divided on the issue and unable to agree on an immigration plan.
Many politicians in Donald Trump's party support his government's actions but other politicians both in his party and in other parties, are preparing a new law which would end the separation of children and parents at the border.
Critics have argued that families are being separated because of the Trump administration's decision to criminally prosecute all those who enter the us illegally, leaving any children they brought with them as unaccompanied minors.