The changes came into effect on Sunday, April 30, and will remain in place until Wednesday, June 21, as track upgrades take place.
V/Line is asking passengers to allow up to 50 minutes extra for the journey while services are disrupted.
Trains will continue to operate between Bendigo and Southern Cross.
For Epsom passengers, services which usually originate or terminate at Echuca and stop at Epsom will be replaced by coaches, but services which originate or terminate at Epsom will continue to run as trains.
A dedicated taxi replacement service will be in place for passengers travelling to and from Huntly Station.
Passengers are encouraged to download the temporary timetable from the PTV or V/Line websites, as coaches will depart Echuca up to 15 minutes earlier than the usual train schedule to ensure connection with trains at Bendigo.
During this time, crews will reconstruct and repair track formation, replace 15,000 sleepers and more than 50,000 tonnes of ballast, and upgrade bridges and drainage.
A V/Line spokesperson said the upgrades would improve reliability and pave the way for trains to run at faster speeds along sections of the track in the future.
The Bendigo and Echuca line upgrade has delivered three new stations and has tripled the number of services on the Echuca line.
Passengers are encouraged to visit ptv.vic.gov.au/disruptions for more information and to plan their journey.