"I, the engineer, Abdo Hussameddin, deputy oil minister,
announce my defection from the regime and my resignation," he said in a video recorded statement, which activists have posted on YouTube.
"I am joining the revolution of the people who reject injustice and the brutal campaign of the regime, which is seeking to crush the people's demand for freedom and dignity," he added.
Hussameddin said he had served in the Syrian government for 33 years, and did not wish to end his life "serving a criminal regime
Hussameddin is now the highest ranking Syrian official to resign from the regime of Syrian President Bashar el-Assad.
The resigning minister's decision came hours after US Secretary of Defense Leon Panetta
announced plans to send non-lethal aid to Syrian rebels to help in the fight to oust President Assad. This is the first time the Obama administration has suggested it was ready to provide direct assistance to Syrian rebels.
Panetta told the Senate Armed Service Committee that the US government is opposed to using unilateral military action, and will pursue diplomacy to force President Assad to resign.
"We are reviewing all possible additional steps that can be taken with our international partners to support efforts to protect the Syrian people, end the violence, and ensure regional stability. including potential military options, if necessary," Panetta said.
According to the United Nations, more than 7,500 people have died in the violent conflict, which has been going on since early 2011. Those opposing President Assad are severely outgunned, and in desperate need of assistance.
Former UN Secretary General, and current UN Arab League envoy Kofi Annan will visit Syria Saturday to speak with government officials.
The Syrian government has yet to comment on Hussameddin's announcement.