According to initital reports, unknown assailants opened fire on a car which carried both of them as they exited the former Nazim's home in North Nazimabad. They were both killed on the spot.
Police said the assailants managed to escape after committing their deed.
The friend was identified as former first-class cricketer Khalil Ullah.
Their bodies have been moved to the Abbasi Shaheed Hospital.
Dr Mehmood was a central leader of the Jamaat-e-Islami and had been elected a Nazim in 2001.
Karachi has been gripped in a spate of target killings, with three activists of the Pakistan Peoples Party (PPP) being gunned down near Matric Board Office within the North Nazimabad police station remits on September 13.
The victims were identified as Mairaj Khattak, 45, Waseem Khattak, 35 and Sultan Gilgiti, 40.
According to a recent National Assembly briefing by Interior Minister Rehman Malik, 1,363 people have lost their lives at the hands of target killers during the past five years.
Giving a breakdown of the figure, Malik said that 104 people had been killed in year 2008, 160 in 2009, 373 in 2010, 478 in 2011 and 248 so far in 2012.
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