The Grade II listed building originally opened in 1856 but was damaged by a fire in 1972.
It closed in 2012 so a proper stage, backstage area and additional performing spaces could be built. The seating capacity has also increased.
An adaptation of the Great Gatsby will be the first production to be shown at the renovated theatre.
The University of Portsmouth is leasing part of the site from the theatre and will teach from the building.
A performing studio and rehearsal space has been built on land behind the theatre and is dedicated to the late director Anthony Minghella.
Caroline Sharman, artistic director and chief executive, said: "Over the past 40 years, there have been various attempts to keep it going.
"The support we got from the community has been hugely important.
"The more people I have spoken to the more I have heard what it means to people, such as their grandparents meeting here or getting engaged in a box.
"I am looking forward to welcoming people and saying thank you. It's really important for me to just say thank you to everyone."
The New Theatre Royal will feature in the documentary 'On Stage' on  9 November at 19:30 BST on BBC One in the south of England.
The New Theatre Royal in Portsmouth is reopening after a £4.5m revamp.