The court's decision comes four years after the initial sentencing of 32-year-old Tomohiro Kato, who drove a truck into a crowd of shoppers in central Tokyo in 2008 before he began to stab passers-by.
During Kato's trial in 2011, a judge described the 2008 killing spree as "a brutal crime that did not show a shred of humanity on the part of the defendant."
The judged added that the death penalty was the only suitable punishment for Kato, who said, in turn, that he had committed the crime because he had allegedly been the target of online bullying.
"I wanted people to know that I seriously wanted to stop the harassment on the Internet bulletin board I was using," Kato said.
It was not immediately clear when he would be executed.
International human rights groups have repeatedly criticized Japan's judicial system, stating that the country's death row inmates wait for their executions for years in solitary confinement.
Currently, Japan reportedly has more than 100 inmates on death row.
The vast majority of those condemned to death have been found guilty of multiple murders.
