The fire raging on Saddleworth Moor is generating high levels of pollutants that could have a significant effect on people's health, experts have warned.
As firefighters battled the blaze, Manchester Fire and Rescue Service (GMFRS) urged residents to keep doors and windows closed.
The smoke can irritate eyes, skin and air passages, leading to coughing and wheezing, breathlessness and chest pain, and it can also worsen existing problems such as asthma, officials said.
People with asthma should carry their inhaler with them at all times and anyone concerned about symptoms is advised to contact their GP or NHS Direct.
Experts said the fire was generating high levels of tiny particles of pollution known as "particulate matter", created by burning materials such as plants.
The particulate matter is combining with high levels of ozone, another pollutant created when pollution is exposed to sunshine, leading to poor air quality in the area.
Hugh Coe, professor of atmospheric composition at the University of Manchester, said:
"High levels of particulate matter are being emitted from the large moorland fire in north Derbyshire and are affecting large areas of Greater Manchester.
He said pollution plumes have been detected in the centre of Manchester.
Measurements were showing high concentrations of particulate matter, which the instruments identified as coming from burning plant matter and so the moorland fire was the cause.
"These high levels of particulate are mixing with air that already has very high levels of ozone, formed when pollution is exposed to strong sunlight.
"Both of these pollutants have significant health impacts including leading to breathing difficulties, sore throat and eye irritation," he warned.
Alastair Lewis, professor of atmospheric chemistry at the National Centre for Atmospheric Science, University of York, said the main pollution from moorland fires was particles and smoke.
The smaller particles known as PM2.5 can enter the lungs, while particles from burning can carry toxic chemicals on their surfaces, he said.
Dr Thomas EL Smith, assistant professor in environmental geography at the London School of Economics & Political Science, said photos from the eastern suburbs of Manchester suggested "hazardous" levels of particulate air pollution, while data from the city centre indicates "unhealthy" levels.
"People with pre-existing heart or respiratory conditions should be advised to avoid exertion.
"Children and the elderly, even without pre-existing conditions, should avoid exposure to the smoke in the eastern suburbs, where we can clearly see from photos that the smoke is thick," he urged.
Experts also warned that climate change could mean more periods of prolonged dry weather which increases the risk of fires and the kind of air pollution events they bring.