The party's central committee "held a lengthy meeting... on Monday morning," at which "a new national leadership was chosen", the Baath party website said.
It published the names of 16 members of the new leadership, which included none of the party's old chiefs with the exception of Assad.
The website said Assad would remain the party's secretary general.
Sharaa, who has been Syria's vice president since 2006, will remain in office despite his removal from the party leadership.
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Bassam Abu Abdullah, director of the Damascus Centre for Strategic Studies, said the overhaul was the result of deep-seated discontent within the Baath party.
"There has been a lot of criticism from within the base towards the leadership, which has been accused of being inflexible, both before and since the crisis," he said, referring to the Syrian uprising.
"A complete change indicates the failure of leadership and the dissatisfaction from within the Baath party base," he told AFP.
A second Syrian analyst, speaking on condition of anonymity, said the reshuffle was as a result of "the old leadership's inability to take the initiative and confront the crisis".
"They've decided to bring in a younger leadership that is seen as more open to the international community," he told AFP.
The overhaul means that for the first time none of the members of the party's leadership is a member of the Syrian intelligence forces.
The Baath party has been in power since March 8, 1963 and is the most powerful political party in Syria.
Today's meeting of the party's central committee was the first since 2005, when much of the previous old guard was replaced.