People living or working in the Lower Cynon Valley - which includes Abercynon, Penrhiwceiber and parts of Mountain Ash and Aberaman - will be offered tests.
Test centres will run from Saturday until 20 December.
It is the second place in Wales to have mass testing after Merthyr Tydfil.
Residents in Mountain Ash East and West, and Aberaman South residents, are also eligible for the tests, which give results in 30 minutes.
Cwm Taf Morgannwg health board public health director, Dr Kelechi Nnoaham, said: "The rate of Covid-19 infection is still very high in our communities, and by engaging with this testing programme, people in the Lower Cynon Valley can play a major role in protecting everyone in our communities."
The main test centres are at Cynon Valley Indoor Bowls Centre, Mountain Ash and Abercynon Sports Centre.
John Collins, 88, from Penrhiwceiber, who took a test at the bowls centre, said: "At my age you have to try and avoid getting this virus."
The testing programme will use so-called lateral flow devices which can get results in about 20-30 minutes.
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If a person tests positive, they will be asked to return home so they can self-isolate immediately.
Concerns have been raised by some experts that people who are declared negative could have a misplaced sense of reassurance.
If someone tests negative, they should still follow the rules, and maintain social distancing, hand hygiene and mask wearing.
Rhondda Cynon Taf council leader Andrew Morgan said about 27,000 people could be tested in the Lower Cynon Valley.
"Unfortunately, over the last week or so, we are seeing our cases starting to increase at quite a concerning rate," he told BBC Radio Wales Breakfast with Oliver Hides.
He said the area had seen 300 positive cases in the last two days so it was "important" to identify and isolate those who were asymptomatic within communities to break "chains of transmission".
"This is an integral part of our fight against the virus, as it gives us a greater understanding of the prevalence and level of transmission within our communities," he said.
Health Minister Vaughan Gething said: "I would encourage the people of Lower Cynon Valley to get tested."
The Merthyr pilot for mass testing, which launched last month, will run until 11 December.
The case rate in Rhondda Cynon Taf (RCT) is 368.5 per 100,000, reporting 889 new positive tests in the past week.
The south Wales valleys had been dominating for highest case rates and having fallen back early in November, the rates have now started to move up again.
In the most recent comparable week, Torfaen, Blaenau Gwent and Neath Port Talbot have been among the 10 highest case rate areas in the UK.
“This last is important. Even in corporate environments, it is very difficult to remove an underling for incompetence if that underling has seniority and a long history of good performance reviews. As in government bureaucracies, the easiest way to deal with such people is often to “kick them upstairs”: promote them to a higher post, where they become somebody else’s problem.”