"The children will have a magical moment of entry," museum president and chief executive Crystal Bowyer said of the multiple-storey Dream Machine, a structure of slides and climbers that starts the adventure.
"We wanted to weave all the Steam concepts, incorporating the arts into Stem (science, technology, engineering and mathematics) through dreaming."
The museum will open with a gala party on November 1 and a family event the next day. Tickets for the fundraising celebrations range from US$75 to US$750 for various events.
From November the museum will be open daily, tickets will be sold online and it hopes to attract about 500,000 visitors annually.
Originally named the Capital Children's Museum, the institution opened in 1974 in a former convent.
Congress designated it the National Children's Museum in 2003, and a year later the museum sold the property it had long outgrown for US$25m. The plan was to reopen in a 13,000sq m space designed by architect Cesar Pelli at L'Enfant Plaza in 2008. That project never happened, nor did a second iteration of Pelli's design on donated land at National Harbour in Maryland.
The museum opened the Launch Zone at National Harbour in 2009 to keep a physical presence while it sorted out its future.
A larger space opened in 2012 but closed three years later. Since 2015, the museum has been a virtual one, creating programmes for public schools and public libraries.
"It's a blessing in disguise that that didn't happen," Bowyer said of the Pelli construction. "The operating costs were too high."
The museum's exhibition space is on par with other children's museums, Bowyer said.
"We have big plans for the future," she said, "but this is our first step, getting the doors open and having these magical experiences for the kids."