More than 40 homes will be demolished to make way for the Galway bypass, with the university campus and Ballybrit racecourse to also be affected by the newly-chosen route.
A further 10 homeowners will be severely disrupted by the plans and will also receive offers to buy their properties.
Castlegar village will be significantly affected by the route, as will sections of the N84 Headford and N59 Moycullen roads.
The €500m bypass route will also affect lands owned by NUI, Galway in Dangan and the Galway Racecourse in Ballybrit.
While a number of stables will face demolition to make way for a cut-and-cover tunnel, it will not affect the racecourse itself. However, manager John Moloney said he was concerned about the possible loss of stables and disruption to the track during construction.
Eileen McCarthy of engineering firm Arup confirmed the racecourse was one of two businesses that was "very severely impacted" by the plans, along with a Vodafone mast on the Cappagh Road.
NUI Galway also raised concerns about the route, which cuts through the hurling pitch and a training area with planning permission for a floodlit facility.
A university spokesperson said the chosen route would have a very significant impact. "The university will obviously have to examine the latest proposal in detail and consider all available options to protect its strategic interests. This is a very disappointing outcome," he said.
The route includes two tunnels, a viaduct and three major intersections, at Briarhill, the Headford Road and Letteragh in Rahoon. One tunnel will cut through the top of the racecourse with a second tunnel at Coolagh close to Lackagh quarries.
The road will continue via bridge and viaduct across the Corrib south of Menlo castle. It will become a single land route at Letteragh, bypassing Bearna village before tying into the R336 Connemara road. It will also connect to Knocknacarra and the Parkmore and Ballybrit industrial estates.
Three homes will be demolished in Bearna, one on the Ballymoneen Road, three in Letteragh, one on the Heath, eight on the N59, one on the Dyke Road, 11 on the N84, nine in the Castlegar area, three on the N17 and one on the Monivea Road.