Winfrey donated more than $1 million to the center and narrates an interactive film focusing on Ohio and Kentucky abolitionists.
The star-studded grand opening gala will be held in a football field-sized tent erected on Cincinnati's revitalized riverfront Sunday night. More than 1,300 tickets have been sold, the Cincinnati Enquirer said.
First Lady Laura Bush will dedicate the Freedom Center Monday night.
The 158,000-square-foot museum, like the National Holocaust Museum in Washington, takes visitors on a journey through history, in this case from the Underground Railroad that helped thousands of slaves to freedom before and during the Civil War to modern liberation movements in Africa and Europe.
The $110 million Freedom Center museum opened its doors to the public Aug. 3.