Ganguly, who hurt his back during fielding in the final One-day international, will return on April 1 to consult a specialist doctor back home in Kolkata.
The second Test begins in Lahore on April 5.
The Indian team management has requested the services of One-day middle order batsman Mohammad Kaif in place of Ganguly.
"Physio Andrew Leipus has been working with Ganguly for the past few days but he has shown no sign of improvement," team manager and Board of Control for Cricket in India (BCCI) joint secretary Prof R S Shetty said in Multan on Tuesday.
"Therefore it has been decided that Ganguly will return home to consult a specialist (doctor) in his hometown."
But Shetty said Ganguly was not ruled out of the entire series and could play the third Test starting in Rawalpindi on April 13.
"Ganguly will be eligible to play in the third Test if he recovers completely."