The City of Guelph says a stretch of Macdonell Street into the downtown core will be closed on weekends until the end of October.
The road between Elizabeth and Wellington streets will be off-limits while Metrolinx replaces the train bridge over the Speed River.
The work is all in an effort to bring two-way, all-day GO train service into and out of the city. Work is also planned for later this year on the train bridges over Wilson Street and Norfolk Street.
Along with vehicles, the city said people walking and biking will not be able to get through Macdonell Street from 9 p.m. Friday until 12:01 a.m. Monday.
The city added that it has also granted crews an exemption from its noise bylaw, which will allow for overnight work.
Metrolinx said the work is being done during weekend overnights so there is no impact on GO schedules along with VIA Rail and CN trains.
The weekend closures will begin this Friday and continue until the end of October, but the stretch will be open over the Thanksgiving long weekend.
The intersection of Macdonell, Arthur and Elizabeth streets will also be closed to all traffic on these weekends.
The intersection at Macdonell and Wellington/Woolwich streets will be closed to all traffic on the last weekend of the project.
Heavy trucks will have to access the downtown core from the west side using Victoria Road, Stone Road and the Hanlon Expressway.
The city said trucks will not be permitted to access the downtown core via the Macdonell Street bridge or other nearby residential streets.
All other traffic should detour using Stevenson Street, Eramosa Road and Woolwich Street.
Pedestrians and cyclists can use the Heffernan bridge to the north or Neeve Street to the south as an alternate route.