Vieira, who had endured tense relations with the military establishment following disputes over his party's victory in parliamentary elections last November, had escaped a previous attempt on his life last year.
Jean Ping, the chairman of the African Union (AU), said: "I was deeply shocked ... to hear of the assassination. The AU and myself firmly condemn this criminal act."
|A bomb killed General Na Waie hours before the president was assassinated [AFP]
The killing was "serious notably because it comes at a time when efforts were under way to bolster peace following the November election", he said.
Jan Van Maneen, the honorary consul for the UK and the Netherlands in Guinea-Bissau, told Al Jazeera: "Bissau is absolutely calm. There is no fighting; no shooting.
"The constitution says if the president is no longer available, the president of the assembly [parliament] will take over as leader for three months and there should be new elections.
"The thing is that we had elections in November, and the new president of the assembly is a very young man with little experience. We are not sure if he is going to respect the constitution."
He ruled out the possibility of the army seizing power, saying: "The rivalry is now over and maybe it [the assassination] is now the beginning of a new solution."
The army said in a statement it would respect "constitutional order" and called on the population to remain calm.
One of Na Waie's bodyguards said the bomb that killed the general had been placed under a stairway leading to his office.
"He had just reached the first steps when the bomb was triggered. He was mortally injured," the bodyguard said.
Government troops closed down roads around the army building and shut down five private radio stations after the attack.
Guinea-Bissau has lurched from one political crisis to another since independence from Portugal in 1974 and Na Waie's predecessor, General Verissimo Correia Seabra, was shot dead by soldiers in October 2004.
Na Waie served in the military government that overthrew Vieira in the 1990s and was critical of him after Vieira was voted back to the presidency in 2005.
Analysts say instability has been worsened by the presence of international drug trafficking organisations which use the country as a staging post for smuggling cocaine into Europe.