Maryborough and Surrounds is accessible by road  from a number of directions.

The journey is approximately a 2 hour drive either via the Calder Highway and Castlemaine or the Western Highway via Ballarat. The Pyrenees Highway also passes through the town connecting it to other parts of the state. Maryborough is a one hour drive from both Bendigo (along the C277) and Ballarat via Highway C287 through Clunes.