“There was a huge bang then I saw the bus in a mangled heap,” Mohammad Tahir, a witness, said.
“Body parts were scattered across the road and there was blood everywhere.”
The second bomb blast happened about 3km away in the Royal Artillery bazaar.
Security officials said it was timed to target army officers who use the route to reach the military headquarters.
Pakistan has suffered a string of attacks since the security forces crushed armed students at the Red Mosque in Islamabad and a peace agreement in the North Waziristan region broke down in July.
“Today’s attack was in the heart of the high security zone. This cannot be allowed to go on and measures have to be taken to ensure political stability,” Ijaz-ul Haq, religious affairs minister, said.
Brigadier Javed Cheema, interior ministry spokesman, said “both suicide blasts are interlinked and acts of the same network”.
He said that the “tentacles” of the recent violence extended to Pakistan’s tribal areas on the border with Afghanistan.
There was no immediate claim of responsibility for either bombing.
Cheema said the authorities were examining whether Tuesday’s attacks were linked to the two suicide attacks in Islamabad in July that killed 31 people.
“But the demand on Pakistan has always been ‘do more, do more’. Now Pakistan is paying the price of doing more.”