The Tel Aviv court sentenced the Fatah leader on charges of involvement in incidents leading to five Israeli deaths.
Two other 20-year terms for being a member of a banned organisation were also handed down by the same court on Sunday.
The Palestinian Authority has dismissed the sentences as illegal and invalid.
Palestinian Negotiations Minister Saib Uraiqat said: “This sentencing of Marwan Barghuthi is illegal and invalid because the Israeli court has no power to sentence him as an elected member of the Palestinian Legislative Council.”
An Aljazeera correspondent in Palestine said members of the Palestinian Legislative Council, Barghuthi’s wife, citizens of Ram Allah and other supporters have expressed their shock and dismay at the sentencing.
“We ask Israel to release him immediately,” said Qaddura Faris, minister without portfolio in the Palestinian cabinet.
“Everything was illegal from the beginning and the occupation is illegal so the decision is illegal,” Faris said.
Israel‘s real intention in trying Barghuthi was to send a strong message to the Palestinians about the intifada, he said.
Barghuthi’s lawyer said he would not appeal against the sentence.
As he was led away he chanted that ”the intifada will triumph”, raising his manacled hands in a victory sign.
He is the most senior Palestinian to have been tried, convicted and sentenced by an Israeli court.
Barghuthi is a longtime advocate
Barghuthi arrived at the court wearing his brown prison jump suit, surrounded by police and prison guards. He raised his hands into the air, waving V signs. However, when he tried to talk to reporters, he was pushed into the building by the guards.
A lawmaker in the Palestinian parliament and head of the Fatah movement in the occupied West Bank, Barghuthi was snatched by Israeli troops two years ago.
Israel says he played a leading role in the al-Aqsa Martyrs Brigades, which it holds responsible for the deaths of Israelis during more than three years of fighting.
Barghuthi has denied he was involved in violence.
In the end, the court convicted him of incidents leading to five deaths, and acquitted him in the other cases. “He did not have direct control over the militants, but did wield influence,” the judges wrote.
Barghuthi was convicted of a role in three shootings involving a Christian monk in the West Bank in 2001, an Israeli near the Givat Zeev settlement in the West Bank in 2002 and three people at a Tel Aviv restaurant in 2002.
He was also convicted on one count of attempted murder for a botched car bombing at a Jerusalem mall and a separate count of belonging to a banned organisation.
He is a longtime advocate of a Palestinian state alongside Israel and has said peace is possible once Israel withdraws from the occupied West Bank and Gaza.