The Newcastle Bus Interchange was officially unveiled on Sunday at the old Store site in Newcastle West.
The NSW government said it was the "final transport link" for its $650 million Revitalising Newcastle program.
"This is a significant milestone for Newcastle with the fully integrated transport hub connecting buses, coaches, heavy rail and light rail," Transport for NSW's Pete Allaway said.
"Around 300 buses will utilise the interchange on a weekly basis allowing passengers to easily connect to other transport modes."
Mr Allaway said Newcastle had embraced the light rail and "this new interchange will help encourage the use of public transport in the region".
Hunter and Central Coast Development Corporation chief executive Valentina Misevska said the bus interchange would be "a vital part" of a connected city.
"Linking people with places to work, live, stay and play is key to the Revitalising Newcastle program. The bus interchange will now make it easier than ever to move around our city."
Pedestrian access is available between the station concourse, bus interchange, Hunter Street and Stewart Avenue.
The bus interchange will be used by Newcastle Transport's Route 22 bus service, regional bus service operators and coaches servicing Port Stephens, western Lake Macquarie, the mid-north Coast and Cessnock.
Doma Group built the interchange below a multi-level car park for tenants of adjoining 30-storey towers.
Workers have been on site for almost two years, demolishing the Store building and remediating land before constructing the interchange and car park.
Work is still happening on the Store redevelopment and some parts of the new bus interchange, including the kiss and ride area.
Meanwhile, changes to Opal fares begin on Monday.
The cost of light rail during peak periods will rise from $2.24 to $3.20. Bus trips up to three kilometres face the same rise. In off-peak times, these bus and tram fares will drop from $2.24 to $1.60. Off-peak trips between 3-8 km will drop from $3.73 to $1.86 and journeys more than 8km will fall from $4.80 to $2.40.
Transport Minister Andrew Constance has linked the changes to incentives to "help stagger essential travel" during eased COVID restrictions.