The result ensured Serbia won Group Seven with a match to spare and reached their first major tournament as an independent nation. They played in the 2006 finals as Serbia & Montenegro.
Striker Nikola Zigic headed Serbia into a 37th-minute lead before second half goals from Marko Pantelic, Zdravko Kuzmanovic and a late Milan Jovanovic brace completed the rout.
Zigic struck against a subdued Romania from Milos Krasic's corner and the home side ran riot once strike partner Marko Pantelic drilled in the second five minutes after the break.
Serbia coach Radomir Antic, who took over from Miroslav Djukic only two weeks before the qualifiers began in 2008, was elated with his team's success.
"We have written a new page in Serbia's soccer history and the authority we have shown throughout the qualifying campaign gives us plenty of reason to believe that we have a very bright future," he told a news conference.
"Days like this make life worth living and we're absolutely delighted. This is a generation of good players and great characters... they deserve the lion's share of the credit for bringing so much joy to the entire nation."
"We've done a fantastic job and I think we have earned our spot in South Africa with consistent and high-quality performances throughout the campaign," he told Reuters.
"But it's too early to say how far we can go in the finals, there is a long way to go until it starts and what we need to do is keep up the good form and steer clear of injuries.
"Tonight's game was an opportunity we simply had to take and the opening two goals really took the pressure off."
