The fashion retailer has signed a deal to relocate to the entrance of St George's Shopping Centre in Preston from its current site on Fishergate.
The newly renovated 10,000 sq ft store is in the old Dorothy Perkins, Burton's menswear and Next units, on a 10-year lease from landlord Aviva.
The units will be combined to include new sales floor areas across two levels and a new full-width shop front on the high street. The existing River Island store will remain open until the work is complete, expected to be in autumn 2013.
Bosses at River Island have been in ongoing discussions with the shopping centre's owners over the past year to secure the new location, which has been empty for ten months.
Andrew Stringer, general manager of St George's Shopping Centre, said: "The move is fantastic news for St Georges and for Preston as another prime retailer commits its long term-future in the city centre.
"It's taken a long time to conclude but we are delighted that construction work is to commence."
A River Island spokesperson said: "St George's has a strong retail position and is the perfect location for our new-look store which we are sure will attract thousands of shoppers."