The warrant for al-Zawahri, who heads the Egyptian militant movement Islamic Jihad and is believed to be operating in Afghanistan, was issued at the request of the Egyptian authorities.
Interpol has asked its 179 member countries to help track him down.
The international police organisation said al-Zawahri was believed to have masterminded several terrorist operations in Egypt and was "emerging as one of the key figures in Osama Bin Laden's al-Qaeda terrorist network".
Israeli intelligence has named him as the "operational brains" behind the 11 September attacks on the World Trade Center and the Pentagon, which Washington says Bin Laden organised.
He is thought to have played a central role in forging a coalition between the Egyptian Islamic Jihad and al-Qaeda in Afghanistan.
Incriminating associations
He appeared in a video alongside Bin Laden threatening retaliation against the US for the detention of an Egyptian man in connection with the 1993 World Trade Center bombing and in 1998, he was the second of five signatories to Bin Laden's 1998 "fatwa" calling for attacks against US civilians.
He has also been named as the leader of a faction of Islamic Jihad which was thought to have carried out the massacre of foreign tourists in the southern Egyptian town of Luxor in 1997 and is listed on the US Government's indictment sheet for the 1998 US embassy bombings in Kenya and Tanzania.
Furthermore, he is named in European legislation on financial sanctions against the Taleban and in documents produced by the US Treasury's office for foreign assets control.
Giles Foden, author of a forthcoming book on the 1998 US embassy bombings in Kenya and Tanzania, says some analysts believe the Egyptian doctor now controls much of al-Qaeda's finance operations.
Criminal history
He already has a high-profile criminal history.
He was put on trial for taking part in the 1981 assassination of Egyptian President Anwar Sadat and was convicted of illegal possession of arms, serving a three-year sentence.
And then in 1999 an Egyptian court sentenced him to death in absentia for activities related to Islamic Jihad.
Interpol said it had issued a "red notice" high-priority warrant for his arrest - one of about 800 the Lyon-based police organization circulates each year.