"I appeal to all democratic forces to come and save Pakistan," he said. Zardari did not hint as to who was behind the attack.
Reports said a suicide bomber drove a lorry packed with explosives into the entrance of the hotel.
Many foreigners stay in the hotel while visiting Pakistan and it is heavily guarded.
The blast resounded through Islamabad.
There were fears the death toll could rise as many people were feared trapped in the hotel, which is close to the national assembly.
Kamal Hyder, Al Jazeera's correspondent reporting from Islamabad, said it is "probably the most powerful explosion [in Pakistan] in recent times".
He said among the wounded were five Americans, two Saudis, one Afghan, one Libyan and more than 170 Pakistanis.
"Fires are still raging and no one knows how many people have been killed in the explosion."
Hyder said ambulances were still arriving at the scene, indicating that there "must be high casualties indeed".
"Whoever is responsible for this attack chose his target carefully; a very professionally carried out job," he said.
Talat Masood, a military analyst, told Al Jazeera that the attack was "well-planned and co-ordinated".
Imran Khan, also reporting for Al Jazeera, said he had seen bodies removed from the scene of the explosion and that the hotel was in danger of collapsing.
He said the driver of the vehicle didn't go through the security checkpoint.
"This is a massive explosion. Fire is spreading very quickly and has taken over the entire hotel," Khan said.
P J Mir, a political and security analyst, said to Al Jazeera: "This is Pakistan's 9/11. Because the Marriott [hotel] has been the focal point of any [political or diplomatic] .... event.
Mir said that as the attack was in the centre of the capital, "[it] is a clear message that the extremist element in that area is not going to stop at anything."
The US and Britain, both at the forefront of the "war on terror", also condemned the attack.
Gordon Johndroe, the White House spokesman, said: "The United States strongly condemns the terrorist attack ... The United States will stand with Pakistan's democratically elected government as they confront this challenge."
David Miliband, the British foreign secretary, said it was a "disgraceful" attack and that it reinforced Britain's to resolve violent extremism.
The Islamabad bombing came on the heels of another which left at least eight Pakistani soldiers dead in a suicide attack on a military convoy in the country's northwest tribal region.
The attack took place as the troops passed through North Waziristan on Saturday, a security official said.
"Eight soldiers have died and some 12 others were injured," the official said, adding the death toll may increase.
Al Jazeera's Hyder said many soldiers had been killed in attacks in the area before.
"This attack occurred on a stretch of road that has become known as IED-ally," he said, referring to the acronym for an improvised explosive device.
|A blast on Friday in Quetta at a religious school killed five students [AFP]
North Waziristan, which borders Afghanistan, is a sanctuary for al-Qaeda and Taliban fighters and has been the scene of fierce battles and suicide attacks over the past several years.
A large number of Arab and Central Asian fighters linked to al-Qaeda are reported to be hiding near the town of Mir Ali, the site of Saturday's attack, officials said.
Pakistan's new government has committed itself to the US-led campaign against the fighters even though the campaign is unpopular throughout the country.
A senior official in the administration of George Bush, the US president, said on Friday Pakistan was not equipped to combat the fighters.
"This is a problem that's been created in sovereign Pakistani territory and the problem is going to be solved when Pakistan has an ability to exercise control over that territory," Stephen Hadley, Bush's national security adviser, said.
"We recognise that in the short term right now there are threats emanating out of that area that threaten Pakistan, that threaten our troops in Afghanistan and potentially threaten the homeland."