The Pakistan Meteorological Department warned the sweltering heat would continue throughout the week, forecasting daytime temperatures of between 40-43 degrees.
"Considering the ongoing observance of Ramadan and people fasting, authorities have to ensure adequate supply of power and water," the department said in a statement.
Karachi mayor Waseem Akhtar urged residents to stay indoors during the day to avoid heatstroke.
Still thousands remained outdoors where they huddled around public taps, wetting towels to cover their heads.
The city of more than 15 million is hit by frequent power cuts and has few green spaces.
People living on its streets have little access to shelter or safe drinking water, making them acutely at risk in blistering temperatures.
The heatwave coincides with the beginning of Ramadan, when millions of devout Pakistanis abstain from food and drink from sunrise to sunset.
In June 2015 about 1,200 people died in southern Pakistan during a heatwave, with nearly two-thirds of the victims homeless people.
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