It branched from the M4 at junction 43, just west of Neath. It ran north-east, bypassing Resolven before reaching Glyn-Neath, from where it curved south-east around the southern edge of a national park. It then curved back around north-east to Merthyr Tydfil, where it intersected with the A470. After continuing through the north of Merthyr Tydfril, the A465 ran north-east, traversing the south east corner of the national park to reach Abergavenny, where it crossed the River Usk and intersected with the A40. From Abergavenny, it continued north, through the national park.