The panel, which interviewed 223 victims and witnesses including defectors, called on Syria to halt the "gross human rights violations", release prisoners rounded up in mass arrests and allow media, aid workers and rights monitors access to the country.
Syria is "responsible for wrongful acts, including crimes against humanity, committed by members of its military and security forces as documented in the present report," the three-member panel said in a 39-page report to the U.N. Human Rights Council.
It catalogues executions, torture, rapes including of children, arbitrary detentions and abductions carried out since March by Syrian forces quashing pro-democracy demonstrations while enjoying "systemic impunity" for their crimes, it said.
"The commission therefore believes that orders to shoot and otherwise mistreat civilians originated from policies and directives issued at the highest levels of the armed forces and the government," said the team, led by Brazilian expert Paulo Pinheiro.
More than 3,500 people have been killed in the violence, according to the United Nations, while activists say that up to 30,000 have been arrested, many kept in open-air stadiums.
The U.N. Security Council stopped short of taking action against Syria when China and Russia vetoed a resolution in October. After continuing international criticism of Assad's handling of the crisis, the Arab League approved sanctions against Syria on Sunday.
On Monday, tens of thousands of Syrians protested in state-backed rallies against the sanctions, the toughest imposed by the Arab League against one of its own members.