The announcement on Thursday comes a day after an apparent Israeli strike in the Iranian capital killed Hamas' top political leader.
Israel believes Deif, the head of Hamas' military, and Yahya Sinwar, the top Hamas leader in Gaza, were the chief architects of the October 7 attack that killed some 1200 people in southern Israel and triggered the Israel-Hamas war.
Sinwar is believed to remain in hiding in Gaza.
We can now confirm: Mohammed Deif was eliminated.— Israel Defense Forces (@IDF) August 1, 2024
Israel has not confirmed or denied it was behind Tuesday's strike in Tehran that killed Ismail Haniyeh, Hamas' political chief.
Hamas has said Deif survived the July attack in Gaza and did not immediately comment on the military's announcement of confirmation.
The killing of two of Hamas' most senior figures brings a victory for Israeli Prime Minister Netanyahu, who has said he will not end the campaign in Gaza until Israel destroys Hamas' military capabilities.
Israeli Defence Minister Yoav Gallant said the strike that killed Deif was a "significant milestone" toward achieving the goals of the war.
"The results of this operation reflect that Hamas is an organization in disintegration," he wrote on X.
The assassinations risk pushing Hamas to harden its position in negotiations for a ceasefire or to drop out completely.
Muhammad Deif, the 'Osama Bin Laden of Gaza,' was eliminated on 13.07.24. This is a significant milestone in the process of dismantling Hamas as a military and governing authority in Gaza, and in the achievement of the goals of this war.— יואב גלנט - Yoav Gallant (@yoavgallant) The operation was conducted precisely and… pic.twitter.com/WCgL5fBkECAugust 1, 2024
And Iran has vowed vengeance for the strike on its soil, raising fears of an all-out regional war.
Israel targeted Deif in a July 13 strike that hit a compound on the outskirts of the southern Gaza city of Khan Younis.
The military said at the time that another Hamas commander, Rafa Salama, was killed.
More than 90 other people, including displaced civilians in nearby tents, were killed in the strike, Gaza health officials said at the time.
In a statement on Thursday, the Israeli military said "following an intelligence assessment, it can be confirmed that Mohammed Deif was eliminated in the strike".
In its 10-month-old campaign of bombardment and offensives in Gaza, Israel has killed some 39,480 Palestinians and wounded more than 91,100 others, according to Gaza's health ministry, whose count does not differentiate between civilians and combatants.
Israel targeted Mohammed Deif in a July 13 strike that hit a compound outside Khan Younis. (AP PHOTO)
More than 80 per cent of the population of 2.3 million have been driven from their homes, the vast majority crammed into tent camps in the southwest corner of the territory, with limited food and water.
Deif was one of the founders of Hamas' military wing, the Qassam Brigades, in the 1990s and led the unit for decades.
Under his command, it carried out dozens of suicide bombings against Israelis on buses and at cafes and built up a formidable arsenal of rockets that could strike deep into Israel and often did.
He remained a mysterious, underground figure in Gaza.
He never appeared in public, was hardly ever photographed and only rarely was his voice heard in audio statements.
He survived a string of Israeli assassination attempts.