The province, which abuts Iraq, forms part of the IS's newly-declared "caliphate", which it said extends from Aleppo in northern Syria to Diyala province in eastern Iraq.
The Syrian Observatory for Human Rights said the takeovers came after some fighters from rival rebel groups, including Al-Qaeda affiliate Al-Nusra Front, withdrew from the province while others pledged allegiance to IS.
"All towns and villages on the route from Albu Kamal (on the Iraq border) to Al-Bab (in Aleppo province), passing through Raqa province (on the Turkish border), are now under IS control," said Observatory director Rami Abdel Rahman.
He also said Mayadeen, the biggest town in Deir Ezzor province, "is now under IS control, after Al-Nusra Front evacuated its headquarters there, and IS raised its banner."
Only the provincial capital, which shares the same name as the province, and the military airport are not under IS control, Abdel Rahman said. The city of Deir Ezzor is split between President Bashar al-Assad's forces and an amalgam of rebel groups.
The Observatory said the withdrawal of the rival rebel groups followed negotiations between fighters from Al-Nusra Front and IS, mediated by local tribes, "to stop the bloodshed".
Earlier Thursday, some fighters, including members of Al-Nusra Front, distributed a video statement via jihadist forums announcing their "repentance" for battling IS, while renouncing loyalty to the rebel Free Syrian Army and the opposition National Coalition.
Some Syrian rebels initially welcomed IS, formerly known as the Islamic State of Iraq and the Levant (ISIL), among their ranks as they battled Assad's forces in their bid to topple his regime.
But in January, rebels and Al-Nusra Front fighters began turning their guns on IS fighters, whose brutal abuses and quest for hegemony earned them the opposition's wrath.
IS has vastly bolstered its reputation and its resources through an offensive it launched in Iraq on June 9, capturing a swathe of territory in northern and western provinces as it sweeps towards Baghdad.
It has brought many of the heavy weapons it seized from Iraq's fleeing troops across the border and is now deploying them in Syria, giving it vastly improved firepower.
On Sunday, the group declared a "caliphate" straddling Syria and Iraq, referring to an Islamic system of rule that was abolished nearly 100 years ago in a move that has angered other rebel groups and Islamists, who declare it a 'heresy".
Syria's war began as a peaceful movement demanding Assad's ouster, but morphed into a conflict after the regime unleashed a brutal crackdown on dissent.
Many months into the fighting, jihadists started to pour into Syria, drawing warnings from analysts of a looming regional conflagration.