HSBC Bank on Heol Eglwys, 2008
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The place-name Ystradgynlais, meaning 'vale of the river Cynlais' - Cynlais may be a personal name, or derive from cyn ('chisel') and glais ('stream') - is first recorded in 1372. In the 1600s there were only a couple of houses by the church and a pub (now the rectory). In 1801 there were only 993 residents in the town living in only 196 houses. The first documented written evidence of iron working in the area was at Ynyscedwyn and is of a deed of release dated 1729. By 1750 there were seven furnaces in south Wales, one of which was at Ynyscedwyn.
The first written evidence of coal workings in the area was in 1780 in Wauclawdd. Most of the coal dug up in the area was sent to the blast furnaces of the iron works. By 1790 the full extent of the mineral resources in the valley were better known and it was realised that to exploit these to the full, improved transport would be essential.
The greatest increase in population was from 1821-41 which coincides with the coming of George Crane and the development of the Ynyscedwyn Ironworks. By 1870 however the area's industrial development was in decline due to various economic factors. Although coal mining carried on in the area a few light industries have replaced the heavy industries.
Ystradgynlais is one of the few areas within Brecknockshire which has a high proportion of Welsh-speakers; indeed, according to the 2001 census, over half of all the Welsh-speakers within Brecknock district live in Ystradgynlais itself.
Ystradgynlais hosted the 1954 National Eisteddfod, an annual Welsh festival of literature, dance, and music. The century-old award-winning Ystradgynlais Public Band competed in the 2005 National Eisteddfod.
Dan yr Ogof caves are a short journey from the town centre, passing Craig-y-Nos Castle and country park. The caves are reputed to have once been the hideout of folk figure Twm Siôn Cati. Henrhyd Falls are also nearby.
Ysgol Maesydderwen. Ystradgynlais is also home to the Miners Welfare Hall, known and promoted as 'The Welfare', which plays host to a cinema. It also has a number of public houses.
In 2016 The Stephen Lewis Tristars Aquathlon in Ystradgynlais won the Welsh triathlon event of the Year 2016
National Cycle Route 43 passes by the southern edge of the town on the line of the former Swansea Vale Railway which linked Swansea via the Neath and Brecon Railway at Coelbren with Brecon. Ystradgynlais railway station was operational from 1869 to 1923.
- Thomas Levi (1825-1916) was a Welsh, Calvinistic Methodist minister, and literary figure who also played a role in the political life of Wales. Born in Ystradgynlais he spent his later life as minister of Tabernacl, Aberystwyth.
- Madame Adelina Patti (1843-1919), the renowned opera singer who lived at Craig y Nos Castle, was married in the parish church and her body lay there in state after her death.
- Composer Daniel Protheroe (1866–1934), was born in Ystradgynlais and lived there prior to emigrating to Scranton, Pennsylvania.
- Tudor Thomas (1893-1976) was born in Ystradgynlais. Thomas was an early specialist in corneal grafting; he managed to bring sight to a man who had been blind for 27 years. He was knighted in 1955
- The Polish painter Josef Herman (1911–2000), spent 11 years living and painting in Ystradgynlais.
- William Lewis Thomas (1913—1995) born in Ystradgynlais, was a rugby union and rugby league footballer of the 1930s, and 1940s. He played club level rugby union (RU) for Ystradgynlais RFC (captain in 1937/38), and club level rugby league (RL) for Ystradgynlais RLFC
- Sir Goronwy Hopkin Daniel KCVO (1914–2003) was a Welsh academic and civil servant.
- The novelist Menna Gallie (1919–1990) was born here, and later wrote two novels based on the area, Strike for a Kingdom (1959) and The Small Mine (1962)
- John Howard Purnell OBE MA PhD ScD CChem FRSC (1925–1996) was a Welsh chemist. He attended Maes y Dderwen County School in Ystradgynlais. In 1965 he became Professor of Physical Chemistry at University College, Swansea and he was president of the Royal Society of Chemistry between 1994 and 1996.
- Caerwyn Roderick (1927–2011) Member of Parliament for Brecon and Radnor, 1970–79, was born in the town
- Julian Hopkin (born c.1945/8) is a physician, researcher and medical teacher. In 2004, he became the founding Head of the new Medical School at Swansea University. He is Professor of Experimental Medicine at Swansea University Medical School and Honorary Physician at the Abertawe-Bro-Morgannwg University Hospital. Received a CBE in 2011 for his services to medicine
- Rowan Williams, (born 1950) the former Archbishop of Canterbury grew up in Ystradgynlais
- Huw David Richards (born 1960) is a former Welsh and Neath RFC rugby union player. He played in the 1987 Rugby World Cup, as a lock, and became the first player to receive a red card in a Rugby World Cup tournament. Richards was born in Carmarthen and attended school in Ystradgynlais
- Kevin Hopkins (born 1961) a former Wales international rugby player was brought up in Ystradgynlais, attending Maesydderwen Comprehensive School, and started his playing career with Ystradgynlais RFC. He too played for Wales in the 1987 Rugby World Cup.
- Prison reform campaigner Ben Gunn (born 1965) grew up in the town. Convicted of murder at the age of 14, he served 32 years in prison before being released on licence. 
- Grownups actor Steve Meo (born 1977) attended Maesydderwen Comprehensive School in the town.
- It is the hometown of the actress Eve Myles (born 1978) who has starred in Torchwood, Frankie and Belonging.
The town is the home of Ystradgynlais F.C. and Ystradgynlais RFC. Ystradgynlais RFC was established in 1890; they hold a fierce rivalry with Ystalyfera RFC and Abercrave RFC. Players who represented their countries whilst playing for Ystradgynlais and notable players: Vernon Cooper, Anthony Buchanan, Steve Bayliss representing Wales; Jonny Koloi for Tonga, and Stan Wright for the Cook Islands.
In 1946, Smiths Industries Ltd, Ingersoll Ltd and Vickers Armstrong founded the Anglo-Celtic Watch Co. Ltd., which produced watches on the Ynyscedwyn estate on the outskirts of Ystradgynlais. The factory was officially opened by Huw Dalton on 15 March 1947. Vickers Armstrong sold their shares to the other two companies in 1948. The Anglo-Celtic Watch Co. became one of the largest producers of watches in Europe, producing up to 1.25 million watches a year. Employees in the factory were said to be working in the 'Tic toc'. The factory closed in 1980.
- "Community population 2011". Retrieved 9 November 2015.
- Longman Pronunciation Dictionary. 3rd Ed.
- Wyn Owen, Hywel; Richard Morgan (2007). Dictionary of the Place-Names of Wales. Llandysul: Gomer Press. p. 504.
- "National Eisteddfod of Wales - National Eisteddfod". www.eisteddfod.org.uk. Retrieved 2 September 2018.
- Ash, Russell (1973). Folklore, Myths and Legends of Britain. Reader's Digest Association Limited. p. 409. ISBN 9780340165973.
- "Victorian Ystradgynlais - the Swansea Canal". history.powys.org.uk. Retrieved 2 September 2018.
- "Sonia Williams". Retrieved 2 September 2018.
- Hughes, Brendan (2012-10-28). "The childhood killer on falling in love with his prison teacher - Wales Online". Wales Online. Retrieved 24 August 2013.
- Time, Time and Time Again. Author: Geoffrey Evans. Published by: Quinto Press Ltd. ISBN 978-1-905960-07-1
- "Anglo-Celtic Watch Co. Ltd. 1". history.powys.org.uk. Retrieved 2 September 2018.