Approximately following the southern boundary of the Brecon Beacons National Park, the Ordnance Survey Pathfinder guide describes it as the unofficial border between rural and industrial South Wales.

The A465 meets the A40 trunk road in Abergavenny and continues west through the 'Heads of the Valleys' region past Brynmawr, Ebbw Vale, Tredegar, Rhymney, Merthyr Tydfil, Hirwaun, Glynneath and Aberdulais.

Even before the construction of the Heads of the Valleys road began in the 1960s, there were concerns and complaints regarding the capacity and safety of a single carriageway, three-lane design.

The high collision rate on this stretch was the main factor in leading to the construction of the dual carriageway between these points.

[5][6] The highest point (signposted) of 1,350 feet (410 m) is on the Ebbw Vale section which is now dual carriageway and slip roads between Dowlais Top and Tredegar via Rhymney.

In 1994, alternatives were presented for public consultation for the improvement of the 25-mile length between Abergavenny and Hirwaun, connecting the existing A465 dual carriageway link from Swansea to the A40, which is an important part of the route to the M50.

This mainly consisted of widening the existing road to provide a dual carriageway standard with grade-separated junctions (and extra climbing lanes on certain hills) between Abergavenny and Hirwaun.

This was tested at public local inquiry in 1998 after which the Secretary of State for Wales announced the decision to proceed with the scheme in 1999.