Crews arrived around 9:10 a.m. to find the hotel's roof in flames.
They were able to contain the fire in about 20 minutes. There was heavy damage to the roof and space below the roof. Some rooms close to the fire had water damage.
Chris Winter said he was attending a company conference and had just gone into the dining room and ordered breakfast when a staff member ran inside and urged everyone to get out.
"You could just see the fire, as soon as you came out of that dining area -- all you had to do was look up and there was 12-, 15-foot flames coming out of the roof," said Winter, who was visiting from Virginia.
There were no injuries.
The Washington Duke Inn & Golf Club is on Cameron Boulevard just south of Duke University's central campus.
The inn said all business events were canceled until 3 p.m. Doors reopened shortly after 3 p.m.
"We are pleased to share that Washington Duke Inn & Golf Club is open for business, and our guests and employees have returned to the property. We look forward to welcoming guests for holiday parties and special events, as planned, and will continue normal operations through the weekend," the hotel said in a statement Friday afternoon.
Clinton Tierney with Restore Pro Reconstruction said the next step is making sure there isn't water damage.
"The fire department's hosed from the roof so it's come all the way down five floors," Tierney said. "Aso we need to find where all that water is and dry it correctly so we don't have microbial growth."
About 35 firefighters responded to the call. The cause of the fire remains under investigation.