In 1966, a coal waste tip slid down a mountain above Aberfan, south Wales, onto the village school, killing 116 children and 28 adults.
The Green Hollow has been written by author Owen Sheers based on interviews with those involved.
The drama is part of a new season of BBC Wales-produced programming.
The hour-long programme, in the form of a poetry film, will feature high-profile Welsh actors including Michael Sheen, Jonathan Pryce, Sian Phillips and Eve Myles.
Owen Sheers said of the programme: "As well as remembering the circumstances and consequences of the disaster, it became equally important for me to create a portrait of what the village was like in 1966 before tip number seven collapsed on Pantglas School - a thriving, vibrant cultural and economic community - and also to paint a picture of the fortitude and optimism present in the village today."
The programme will be broadcast on the day of the anniversary, Friday 21 October on BBC One Wales and BBC Four.
Also making a return to both channels in October will be Ordinary Lies, the Newport-based drama set in a sports company starring Griff Rhys Jones and Kimberley Nixon.
A Doctor Who spin-off for young adults, Class, will be screened on BBC Three from 22 October, while the Ceredigion-set crime drama Hinterland, which is in its third series, will return in the new year to BBC One Wales and BBC Four starring Richard Harrington.
BBC Wales director Rhodri Talfan Davies said: "These four very special shows provide a glimpse into very different Welsh experiences - from the lives and passions of a Newport workforce to the brooding landscapes of west Wales.
"They showcase the brilliant production and acting talent Wales has to offer, and underline the BBC's commitment to improve the portrayal of Wales on the BBC's networks."
A drama portraying the events surrounding the deaths of 144 people in a Welsh village will be aired to mark the 50th anniversary of the tragedy.