Thirty-seven out of 48 defendants accused of inciting violence and blocking the Qalyoub Highway last year were given life sentences Saturday.
Another 10 defendants, sentenced to death in absentia in June, had their verdicts approved by the country's grand mufti, who according to Egyptian law must review all capital punishment verdicts.
One defendant was given three years in jail.
Among those sentenced to life are Muslim Brotherhood Supreme Guide Mohamed Badie, and leading Brotherhood members Mohamed El-Beltagy and Osama Yassin.
The prosecution also accused the defendants of being members in a terrorist group, vandalising public and private properties, illegal possession of arms, and disrupting the general peace.
The case centred on clashes that took place where two were killed and 13 injured after Qalyoub Highway was blocked in the wake of the ouster of Mohamed Morsi in July 2013.
This is not the first mass death sentence announced against Morsi loyalists, who have been arrested in the thousands since last August.
In March, Minya Criminal Court in Upper Egypt sentenced 529 Brotherhood supporters to death on charges of murdering the deputy commander of the Matay district police station during riots that erupted in the aftermath of the forced dispersal in August 2013 of Islamist protest camps in Cairo and Giza that left hundreds dead.
Militant attacks against security forces escalated since the ouster of Mohamed Morsi, leaving more than 500 officers and soldiers dead.
The Muslim Brotherhood has repeatedly denied involvement in the violence. The group was declared a terrorist organisation last December.
