The changes, which take effect from Monday, include the previous seven fare zones being cut to five, and new zone names replacing the previous numbers.
The new inner "city" zone replaces zone 1, and the nearby "ring" zone replaces zones 2, 3 and 4.
This streamlining would make it easier for users to see how much it would cost to travel to their destination, council support manager Gerard Collings said.
The Brockville-St Kilda; Halfway Bush-St Kilda; Belleknowes-Waverley; Ocean Grove-Ross Creek; and Kenmure services feature new routes and timetables, including a single route for weekdays, evenings, weekends and public holidays.
And extra weeknight, weekend and public holiday services will be introduced for Balaclava, Concord and Shiel Hill.
Go Card users will enjoy a free transfer between routes within the same zone, if transfer occurs within half an hour of the first bus’ scheduled arrival.
Mr Collings appreciated that changes to the network, including some new timetables, would "cause some inconvenience as users adjust to new services".
But the overall changes would "make it easier for people to plan their travel", he said.
The council had employed student "ambassadors" on the buses since Monday to help passengers adjust to changes on the new routes.
