Publisher DC Thomson said a multi-million-pound move to its refurbished Meadowside headquarters is a "vote of confidence" on its future in Dundee.
More than 600 staff working in newspapers, magazines and digital media have relocated from the company's offices on Kingsway East.
Meadowside, which was built for DC Thomson in the early 1900s, originally opened in 1906.
Its newspaper production will continue at the Kingsway printing presses.
The company's titles include the Courier, Evening Telegraph and Sunday Post newspapers, and the Beano comic.
The future of the remainder of the Kingsway site is currently being negotiated.
David Thomson, director and chief operating officer, said: "It's fantastic to be back in the heart of Dundee where we belong, in the centre of a city with such an exciting future.
"The original opening of this building 111 years ago was a major vote of confidence in a flourishing business and a clear statement to the city that DC Thomson was here to stay in Dundee.
"I think the same could be safely said on our return here today."
The Meadowside building is on the former site of Dundee's General Post Office. A 10-storey extension was added to the building in 1963.
Mr Thomson said: "It's a positive time for the city as we see the impressive V&A Museum of Design Dundee emerging on the waterfront, creating an international centre of design for Scotland.
"Many creative and commercial opportunities are being developed in Dundee, such as the Dundee Design Festival in our former print works at West Ward.
"It's great to be back and we're proud to be playing our part in the resurgence of Dundee and its city centre."