"It is the large-scale imprisonment of children and parents for the duration of their immigration proceedings which can go on for years" Merkley told Senior Congressional Correspondent Mary Bruce on the podcast. "And we must not allow America to go back to the philosophy of World War II where we lock up thousands of families for years at a time."
His new book, "America Is Better Than This: Trump's War Against Migrant Families," is centered around his account of visiting detention facilities on the southern border.
Trump and Republicans have called the Flores Agreement a "loophole" which encourages undocumented immigrants to bring their children when trying to cross the border.
The senator disagrees saying, "Flores is a fundamental protection of the health and welfare of children and it is exactly the foundation that was established by the court in the agreement. This administration does not accept that it must provide fundamental protection for children."
When asked about why immigration is such a deeply rooted issue for him, Merkley cited his experience living in developing countries like West Africa and Mexico.
"I can personally connect with what is going on in these countries when they're in severe turmoil that produces refugees fleeing persecution," he said.
In June 2018, Merkley visited multiple migrant detention facilities in McAllen, Texas.
"The kids were being torn out of their parents arms and they were being sorted into these cages there at the facility," he said.
He said that he was initially denied entry to another facility converted from an old Walmart which held 1,500 boys.
Nearly a year after that visit, Merkley introduced the "Stop Cruelty to Migrant Children Act," which would prohibit the separation of families, require facilities to provide hygiene products and medical evaluations for all children taken into custody.
In 2013, a major piece of immigration legislation passed the Senate, with four Democrat senators and four Republican senators coming together to craft the bill which passed with a super majority. One of those Republicans who worked across the aisle was Sen. John McCain.
Nearly a year after the senator's death, ABC News Chief White House Correspondent Jonathan Karl sat down with Cindy McCain to talk about her late husband's legacy.
"John was always fighting for the little guy … what we're sorely lacking right now is his voice of reason," she said. "The ability to work across the aisle on these issues. That's how we worked for so many years and now to just close on the ranks and not talk to anybody -- it doesn't make any sense."
A portion of that interview was played for Merkley on the podcast. He agreed with Cindy McCain's assessment and that the Arizona senator worked with Democrats to help craft an "extensive fix to a broken immigration system."
Powerhouse Politics podcast is a weekly program that posts every Wednesday, and includes headliner interviews and in-depth looks at the people and events shaping U.S. politics.
Powerhouse Politics podcast is hosted by ABC News Chief White House Correspondent Jonathan Karl and ABC News Political Director Rick Klein.