The route starts on the A50 to the south of Knutsford and heads southwest through Smithy Green before passing Lower Peover. After running roughly parallel to the M6 for a short distance, it goes over the motorway. It then passes Shakerley Mere before reaching the B5082, which is crossed at a staggered crossroads.
The road continues vaguely southwestwards across the flat Cheshire countryside. It goes through the unusually named hamlet of Puddinglake and crosses the River Dane about a mile further on. The route ends shortly afterwards at a T-junction on the B5309, on the edge of Middlewich.
Before the construction of the B5309 in this area, the B5081 continued ahead before bending sharply left to end on the A54. This section has been destroyed by the building of a new housing estate (with all the roads named after breeds of cattle) but the line of the road can still be seen as an open area heading south from Galloway Close.