It forms the principal route between Bourne and Stamford and the A1 in Lincolnshire, continuing on through Ketton in Rutland to its junction with the A47 at Morcott.

It begins in Morcott at the staggered crossroads with the east-west A47 and the B672 (its continuation to Caldecott), becoming Stamford Road near the White Horse Inn.

From South Luffenham to Caldecott, the A6121 and B672 also follow the Rugby branch of the Syston and Peterborough Railway, which opened in 1851.

From here the road follows the main Syston and Peterborough Railway (part of the Birmingham to Peterborough Line), which it passes under a mile to the east, north of Luffenham Heath Golf Club, and the point where the road crosses the River Chater at Foster's Bridge.

It enters Ketton as Luffenham Road, passing a crossroads for Edith Weston (to the west), and Geeston and Aldgate (to the south).

A railway branch line for the factory passes under the road, and further east is a junction with Steadfold Lane, for Great Casterton, to the north.

On the eastern side of the A1 cloverleaf junction it enters Stamford, South Kesteven, and Lincolnshire as Tinwell Road.

It leaves the main road (Rutland Terrace), following West Street, to the left near a Waitrose.

Further north is the former site of the Mirrlees Blackstone diesel engine works, on the right hand side, now a retail park.