A second shot was heard almost three hours later at 17:00 local time (22:00 BST) when police surrounding building 44 entered to find the gunman and a male hostage dead while a female hostage remained tied up but unharmed.
The stand-off lasted around three hours in total although police investigating the siege believe the male hostage was fatally shot in the chest perhaps minutes into the incident.
Reports also say that frightened staff in the space centre watched the drama onsite unfold on television while they were told via email to stay indoors. A later email told staff to leave the complex when they wished.
It is thought the incident will encourage a review of using agency employees although police say they have no known motive for the killer's actions.
"All of us at Nasa are profoundly saddened by today's tragedy at the Johnson space centre in Houston," said Nasa administrator Michael Griffin.
"Our hearts go out to the families of the victims and all those touched by today's events."
Friday's shooting comes as families continue to mourn those murdered on the campus of Virginia Tech by student gunman Cho Seung-hui.
Fears of copycat shootings have made many nervous in the US, particularly as Friday also marked the eighth anniversary of the Columbine high school massacre which saw 12 students and a teacher shot dead.
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