Danforth Avenue is an east-west street that begins in Old Toronto at the Prince Edward Viaduct as a physical continuation of Bloor Street and continues for about 6 kilometres (3.7 mi) east through old Toronto, about 350 metres (1,150 ft) of old East York, and a further 5 kilometres (3.1 mi) in Scarborough until it intersects with Kingston Road via a ramped interchange.

Previously, Danforth Road continued around the Highland Creek along local residential roadways now known as: The west end of Danforth Ave. spans the Don River valley, the Don Valley Parkway and Bayview Avenue via the Prince Edward Viaduct.

Line 2 Bloor–Danforth of the Toronto subway system runs parallel to most of the road's route, offset to the north some 50 metres (160 ft).

Danforth GO Station, just off Main Street, takes its name from the avenue, where the commuter rail line intersects with it, on the Lakeshore East route.

Danforth is served by the Toronto Transit Commission bus system only east of Main Street Station.

Danforth Avenue was formerly designated as Ontario Highway 5 from the Don River (at Bloor Street) east to Kingston Road.