Some 10,000 tests will be rolled out from Tuesday after four people from two unconnected households were found to be infected with the E484K mutation - nicknamed an 'escape mutation' because it helps the bug slip past the body's defence systems.
Extra screening sites will be set up across Hulme, Moss Side, Whalley Range and Fallowfield with anyone aged over 16 who lives, works or studies in those areas urged to take part – even if they are showing no symptoms.
Volunteers and officials will also be going door-to-door offering to screen anyone who cannot get to a site.
The drastic measures - an attempt to stop the 'escape' mutation taking hold in the wider population- follows similar surge screening in Worcestershire, Sefton, Merseyside, and areas of Bristol and south Gloucestershire, where versions of the Kent variant were also identified there.
It asked for those have already been vaccinated to still get screened. PCR swab tests would be used with results given back within days.
David Regan, public health director at the authority, said: "We all know that the virus will change over time and it's important that we investigate new strains to understand how they might spread.
"This is exactly what we're doing with the intensive testing in parts of Manchester, with local testing units and people going door-to-door to offer people tests."
He stressed there was “no evidence” that this particular variant would be resistant to vaccines or causes a more severe illness.
Bev Craig, the council's executive member for adult health and well-being, said: "It's understandable that some residents in the area may be concerned by all this, but we need to remember that it's very normal for viruses to mutate.
"We are following the public health approach to react to the new variant and we will be working... to ensure as many people as possible know how to get a test so we can understand more about this version of the virus."
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