The scheme, backed by Scottish Government cash, will combine walls, glass panels and flood gates along a new raised walkway to shield the town centre from the River Nith.
Main works are due to kick off in summer 2026 and run through to spring 2028, with landscaping and defects correction works continuing until 2030.
The defences will run from the Dumfries and Galloway Standard offices downstream past Dock Park, with additional barriers across the river at Welldale and Kenmure Terrace.
A Dumfries and Galloway Council spokesperson said the project would not only protect homes and businesses but also transform the riverside into an attractive public space.
The town has long suffered regular flooding, which has damaged property, deterred investment and is expected to worsen under climate change.