The deal, set to be completed at the end of March, will result in a rebranding of the property under a name yet to be confirmed.
It will become the second acquisition beyond its 2,000-acre estate for the five-AA-star, 409-bedroom Celtic Manor, following the purchase of Newbridge on Usk restaurant with rooms in 2010.
Hilton Newport features a restaurant and bar, fitness suite, swimming pool, spa and nine meeting rooms. All staff members will be retained when Celtic Manor takes over the property.
Ian Edwards, chief executive of the Celtic Manor Resort, said: "We are extremely pleased to be exchanging contracts to acquire Hilton Newport and look forward to working with the experienced team there as the hotel transitions to our ownership and management. We are always looking to expand and build upon our successful business at the Celtic Manor Resort while continuing to help support the local community and economy."
He added: "Occupancy at the Celtic Manor Resort is currently running at 90% and there are many nights when we could easily exceed our capacity of 400 bedrooms. The additional bedrooms at the newly-acquired hotel will help address our need for more accommodation across all our markets - conference and business, golf and leisure."
The acquisition will add to Celtic Manor's portfolio of guest residences which include the main resort hotel, the Manor House, the Newbridge on Usk and 10 Hunter Lodges.
As well as being the venue of the 2010 Ryder Cup, Celtic Manor hosted the NATO Summit in 2014. It offers three championship golf courses, two spas and a choice of seven restaurants.