Mrs Bush described the 'zero-tolerance' approach to illegal immigration as 'cruel' and 'immoral'
The US First Lady has appeared to question her husband's immigration policy, amid mounting criticism of families being separated at the US-Mexico border.
Stories of children torn from the arms of their parents have emerged since a "zero tolerance" policy on illegal entries was enforced in April.
An average of 45 children are being taken from their parents at the border each day.
In the last six weeks, it has happened nearly 2,000 times following a White House clampdown.
Melania Trump, in a rare statement on government policy, said the US must be a country that "governs with heart".
In a statement quoted by CNN, a spokesperson for the US First Lady said: "Mrs Trump hates to see children separated from their families and hopes both sides of the aisle can finally come together to achieve successful immigration reform.
"She believes we need to be a country that follows all laws, but also a country that governs with heart."
Former First Lady Laura Bush, meanwhile, strongly criticised the current policy - comparing the border camps to the Japanese American internment camps of World War 2.
Writing in the Washington Post, she argued: "I live in a border state. I appreciate the need to enforce and protect our international boundaries, but this zero-tolerance policy is cruel. It is immoral. And it breaks my heart.
"In 2018, can we not as a nation find a kinder, more compassionate and more moral answer to this current crisis? I, for one, believe we can."
UN High Commissioner for Human Rights Zeid Ra'ad Al Hussein has also voiced his concern over the situation.
He observed: "The thought that any State would seek to deter parents by inflicting such abuse on children is unconscionable.
"I call on the United States to immediately end the practice of forcible separation of these children."
A number of Democratic lawmakers have visited the immigration camps in recent days amid growing outrage.
Senator Jeff Merkley observed: "There is no way that family separation policy is good for anyone.
"This is absolutely un-American and wrong - we must end this policy of family separation."
Other lawmakers have been working to drum up support for legislation barring the practice of children being taken from their parents at the border.
UPDATE: 48 senators now support the Keep Families Together Act. We're making progress, but we still need Republicans to join. If you're represented by a Republican senator, tell them to support S.3036. #KeepFamiliesTogether— Sen Dianne Feinstein (@SenFeinstein) June 17, 2018
President Trump has continued to defend the approach, and pointed the finger at Democrats.
In a tweet overnight, he wrote: "The Democrats should get together with their Republican counterparts and work something out on Border Security & Safety. Don’t wait until after the election because you are going to lose!"
Democrats can fix their forced family breakup at the Border by working with Republicans on new legislation, for a change! This is why we need more Republicans elected in November. Democrats are good at only three things, High Taxes, High Crime and Obstruction. Sad!— Donald J. Trump (@realDonaldTrump) June 16, 2018