The A605 strikes north from junction 13 of the trunk A14 road through the eastern parts of Thrapston, skirts the village of Thorpe Waterville, bypasses Oundle to its east, crosses the River Nene, reaches the eastern limit of the A427 at a roundabout, skirts to the west of Eaglethorpe, crosses into Cambridgeshire near Elton Hall, to reach the A1(M)'s junction 17, whereupon it overlaps the A1 road.

The road split in two just before the A6 with one branch joining the A6 by the Irthlingborough Viaduct and the other at the top of the hill as the A6 enters Higham Ferrers.

The Thrapston Eastern Bypass was opened a few years later running northeast from this roundabout to a new junction with the old A605, just south of the Titchmarsh turn.

This used the alignment of the former BR Northampton to Peterborough railway and crosses the River Nene twice in quick succession.

The road was opened on 12 December 1985 by Princess Alice, Duchess of Gloucester and is commemorated by a plinth and brass plaque at the roundabout.

Beyond Elmington a curve was eased as the road climbed out of the valley and a new straightened section was constructed to a new roundabout for Warmington.

The Elton Bypass climbs two hills and benefits from crawler lanes on both sections from both east and west.

The road passes under the East Coast Main Line and has a roundabout junction with the A15 immediately south of Peterborough city's Nene Bridge.

The road turns south and overlaps the A15 for a short way before originally diverging to the left and passing under the Peterborough Southern Bypass (the A1139) at Stanground.

Around the year 2000 the severely damaged section from Thorpe Waterville to the Lilford roundabout was improved on line.

This was the last section in Northamptonshire to be improved and had suffered badly from HGV with lorry ruts but the work was done on the cheap and the gridded gullies collapsed.

In August 2017 a man from the Peterborough was killed in a collision between two vehicles, a Ford Focus and a Scania lorry, on the A605 near to Haddon services.

The A45 is an east–west road originally from Birmingham to Felixstowe so the north easterly direction of the A605 from the termination of the A45 at Thrapston does not coincide with that of the A45 whereas the A14 now completed that function.