Buses will replace Craigieburn Line trains between Essendon and Broadmeadows from 9pm, Friday, July 22 to the last service on Sunday, July 24.
Buses will then replace all trains between Essendon and Craigieburn from the first to the last service on Monday, July 25, the Department of Transport said.
Passengers are asked to allow up to 40 minutes extra for their journey.
Meanwhile the Department of Transport said Barry Road will be closed between Pascoe Vale Road and Yinnar Street from 5am on Sunday, July 24 to 5pm on Sunday, September 4.
Local access will remain available between Yinnar Street and Sydney Road.
All through-traffic and heavy vehicles will detour using a combination of Sydney Road, Somerton Road, Camp Road and Pascoe Vale Road, the department said.
Local traffic may also use the Riggall Street bridge to cross the train line.
There will be no pedestrian access across the Barry Road bridge while these works are taking place. Nearby alternatives include the overpass at Coolaroo Station to the north and the pedestrian crossing at Smeaton Avenue to the south.
