(CNN) Al Qaeda's second in command, Nasir al-Wuhayshi, has been killed in a drone strike in Yemen, dealing a heavy setback to the leadership of the international terrorist group.

Al-Wuhayshi was the top leader of al Qaeda in the Arabian Peninsula, or AQAP, one of the most dangerous and dynamic branches of the jihadist network.

His death is "the biggest blow against al Qaeda since the death of (Osama) bin Laden ," said CNN terrorism analyst Paul Cruickshank.

Al-Wuhayshi was al Qaeda's "leading light" and was one day expected to take over from its current global chief, Ayman al-Zawahiri , said Cruickshank.

Two Yemeni security officials told CNN on Monday that al-Wuhayshi was killed Friday in a suspected U.S. drone strike in Yemen's Hadhramaut region.

On Tuesday, AQAP released a video statement announcing that its leader and two aides had died. The speaker said that al-Wuhayshi would be succeeded by the group's military chief, Qasm al-Rimi, also known as Abu Hureira al-Sanaani.

'Leadership matters'

The U.S. government confirmed al-Wuhayshi's fate Tuesday, calling his death "a major blow to (al Qaeda's) most dangerous affiliate and to al Qaeda more broadly."

Al-Wuhayshi "was responsible for the deaths of innocent Yemenis and Westerners, including Americans," U.S. National Security Council spokesman Ned Price said.

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"While AQAP, al Qaeda and their affiliates will remain persistent in their efforts to threaten the United States, our partners and our interests, (al-Wuhayshi's) death removes from the battlefield an experienced terrorist leader and brings us closer to degrading and ultimately defeating those groups."

Al-Wuhayshi, known as al Qaeda's crown prince, was a charismatic figure who was adored by many of the terrorist group's jihadist fighters.

In a video that surfaced in April of last year, al-Wuhayshi appeared brazenly out in the open , greeting followers in Yemen, the impoverished nation that the organization uses as a base.

In a speech to the group, he makes it clear that he's going after the United States, saying: "We must eliminate the cross. ... The bearer of the cross is America!"

The video showed what looked like the largest and most dangerous gathering of al Qaeda in years.

Successor seen as 'brains of the operation'

Originally from Yemen , al-Wuhayshi assumed command of AQAP in 2009. He'd escaped a Yemeni prison in 2006 and had previously worked as a personal secretary for Osama bin Laden

His successor is also seen as a formidable leader.

"Qasm al-Rimi was considered the brains of the operation," Cruickshank said. "For more than a decade, he's really been at the helm of the military side of things for AQAP but also planning their large international operations."

The leadership change is expected to bring "a degree of continuity," he said, noting that al-Wuhayshi and al-Rimi were believed to have worked very closely together.

AQAP benefiting from Yemen chaos

Al-Wuhayshi's death comes at a time when AQAP appears to have been thriving amid the recent turmoil in Yemen.

Photos: Unrest in Yemen Photos: Unrest in Yemen The sky over Sanaa, Yemen, is illuminated by anti-aircraft fire during a Saudi-led airstrike on Friday, April 17. The coalition's warplanes have been carrying out strikes against Houthi rebels since President Abdu Rabu Mansour Hadi fled the country in late March. Hide Caption 1 of 42 Photos: Unrest in Yemen A Yemeni boy holds a rifle as Houthi supporters attend a rally in Sanaa, Yemen, on Sunday, April 5, protesting airstrikes carried out by a Saudi-led coalition against Houthi rebels. Hide Caption 2 of 42 Photos: Unrest in Yemen Yemenis dig graves on Saturday, April 4, to bury the victims of a reported airstrike by the Saudi-led coalition in the village of Bani Matar, Yemen. Hide Caption 3 of 42 Photos: Unrest in Yemen Yemenis search for survivors in the rubble of houses destroyed by Saudi-led airstrikes on April 4 in a village near Sanaa. Hide Caption 4 of 42 Photos: Unrest in Yemen Central Sanaa is covered in dust on Friday, April 3. Airstrikes have turned the bustling capital of Yemen into a ghost town. Hide Caption 5 of 42 Photos: Unrest in Yemen A Yemeni man loads a TV set into a van as he prepares to flee Sanaa on Thursday, April 2. Hide Caption 6 of 42 Photos: Unrest in Yemen Militiamen loyal to Hadi take positions on a street in Aden, Yemen, on Thursday, April 2. Houthi rebels seized the presidential palace in Aden, a neutral security official and two Houthi commanders in Aden told CNN. The Houthis are Shiite Muslims who have long felt marginalized in the majority Sunni country. The Sunni Saudis consider the Houthis proxies for the Shiite government of Iran and fear another Shiite-dominated state in the region. Hide Caption 7 of 42 Photos: Unrest in Yemen A framed photo and a purse hang on the wall of a house destroyed by an airstrike near the Sanaa airport on Tuesday, March 31. Hide Caption 8 of 42 Photos: Unrest in Yemen Buildings burn at the Jabal al-Hadid military camp in Aden on Saturday, March 28. Yemeni military officials said an explosion rocked the camp that houses a weapons depot, killing and wounding several people. The camp reportedly had been taken by security forces loyal to former Yemeni President Ali Abdullah Saleh. Some of the forces aligned with the Houthis are also loyal to Saleh, who resigned in 2012 after months of Arab Spring protests. Hide Caption 9 of 42 Photos: Unrest in Yemen Yemeni supporters of the Houthi movement attend a demonstration against Saudi military operations Thursday, March 26, in Sanaa. Hide Caption 10 of 42 Photos: Unrest in Yemen People search for survivors under the rubble of houses destroyed by airstrikes near the Sanaa Airport on March 26. Hide Caption 11 of 42 Photos: Unrest in Yemen Members of Yemen's General People's Committee deploy in Aden, Yemen, on Wednesday, March 25. The militiamen are loyal to Hadi. Hide Caption 12 of 42 Photos: Unrest in Yemen On March 25, honor guards in Sanaa carry the coffins of victims who were killed in suicide bombing attacks several days earlier. Deadly explosions in Sanaa rocked two mosques serving the Zaidi sect of Shiite Islam, which is followed by the Houthi rebels that took over the capital city in January. Hide Caption 13 of 42 Photos: Unrest in Yemen Yemenis stand in front of burning tires during an anti-Houthi protest in Taiz, Yemen, on Tuesday, March 24. Hide Caption 14 of 42 Photos: Unrest in Yemen Medics treat an anti-Houthi protester who was injured during clashes with pro-Houthi police in Taiz on March 24. Hide Caption 15 of 42 Photos: Unrest in Yemen Armed men inspect damage after an explosion at the Al Badr mosque in Sanaa on Friday, March 20. Hide Caption 16 of 42 Photos: Unrest in Yemen A man in Aden holds a police shield that he looted from a base belonging to forces loyal to Saleh on Thursday, March 19. Hide Caption 17 of 42 Photos: Unrest in Yemen Houthi supporters in Sanaa deploy giant national flags Wednesday, March 18, during a demonstration to mark the fourth anniversary of the "Friday of Dignity" attack. In 2011, forces loyal to Saleh opened fire on protesters who had gathered in Sanaa to demand the ouster of Saleh and his regime. Hide Caption 18 of 42 Photos: Unrest in Yemen Supporters of Ahmed Ali Abdullah Saleh, the son of the former President, wave banners and shout slogans during a demonstration in Sanaa on Tuesday, March 10. The demonstrators were demanding presidential elections be held and that the younger Saleh run for office. Hide Caption 19 of 42 Photos: Unrest in Yemen A child raises his fist during a rally by Houthi supporters in Sanaa on Friday, March 6. Hide Caption 20 of 42 Photos: Unrest in Yemen Thousands of armed Yemeni tribal members gather in the southern province of Shabwa on Monday, February 23. Hide Caption 21 of 42 Photos: Unrest in Yemen Supporters of the separatist Southern Movement perform prayers during a demonstration in Aden on Friday, February 13. Hide Caption 22 of 42 Photos: Unrest in Yemen Houthi fighters guard the gate of the presidential palace where a bomb went off and wounded three people in Sanaa on Saturday, February 7. Hide Caption 23 of 42 Photos: Unrest in Yemen Yemeni soldiers guard the presidential palace in Sanaa on Friday, February 6. Hide Caption 24 of 42 Photos: Unrest in Yemen Members of the Houthi movement and their allies attend a meeting in the Yemeni capital on Sunday, February 1. Hide Caption 25 of 42 Photos: Unrest in Yemen Supporters of the separatist Southern Movement flash the victory sign after they seized police security checkpoints on Saturday, January 24, in Ataq, the capital of the Shabwa province in Yemen. Policemen were told to give up their weapons and return to their bases before the militiamen raised flags of the formerly independent South Yemen at the checkpoints. Hide Caption 26 of 42 Photos: Unrest in Yemen Houthi rebels fight with Yemeni protesters during a rally in Sanaa on January 24. Thousands of Yemenis took to the streets of Sanaa in the largest demonstration against Houthis since the Shiite militiamen overran the capital in September. Hide Caption 27 of 42 Photos: Unrest in Yemen On Friday, January 23, Houthis carry coffins of those killed during recent clashes with presidential guard forces in Sanaa. Hide Caption 28 of 42 Photos: Unrest in Yemen A Houthi militiaman sits near a tank near the presidential palace in Sanaa on Thursday, January 22. Hide Caption 29 of 42 Photos: Unrest in Yemen Houthi men wearing army uniforms stand guard on a street leading to the presidential palace in Sanaa on Wednesday, January 21. Hide Caption 30 of 42 Photos: Unrest in Yemen A wounded man rests at a hospital in Sanaa on January 21. He was reportedly injured in fierce clashes the previous day. Hide Caption 31 of 42 Photos: Unrest in Yemen A tank is stationed in front of the Sanaa house of President Abdu Rabu Mansour Hadi on January 21. Hide Caption 32 of 42 Photos: Unrest in Yemen A Houthi rebel mans a checkpoint near the presidential palace on January 21. Hide Caption 33 of 42 Photos: Unrest in Yemen A man walks inside a heavily damaged house near the presidential palace on Tuesday, January 20. Hide Caption 34 of 42 Photos: Unrest in Yemen A woman walks past closed shops in Sanaa on January 20. Hide Caption 35 of 42 Photos: Unrest in Yemen An armed member of the Houthi movement stands guard in the streets of Sanaa on January 20. Hide Caption 36 of 42 Photos: Unrest in Yemen A man surveys his damaged home in Sanaa on January 20. Hide Caption 37 of 42 Photos: Unrest in Yemen Houthis inspect a damaged mosque in Sanaa on January 20. Hide Caption 38 of 42 Photos: Unrest in Yemen Houthi men raise their weapons during clashes near the presidential palace on Monday, January 19. Hide Caption 39 of 42 Photos: Unrest in Yemen Smoke and flames rise in Sanaa during heavy clashes between presidential guards and Houthi rebels on January 19. Hide Caption 40 of 42 Photos: Unrest in Yemen Tribal soldiers protecting the city from Houthi rebels stand guard at the city borders in Marib, Yemen, on January 19. Hide Caption 41 of 42 Photos: Unrest in Yemen Houthi men guard a Sanaa street on January 19. Hide Caption 42 of 42

The group has been "expanding the territory they control, taking advantage of political chaos," Cruickshank said.

AQAP has been feeding off anger among Sunni tribes in Yemen over the advances made by the predominantly Shiite Houthi rebels who overthrew the Yemeni government earlier this year.

Adding to the violence and destruction, a Saudi-led coalition has been bombing the Houthis and their allies in an effort to restore the deposed government.

AQAP has exploited the unrest to seize more turf, including the port city of Al Mukalla, where it freed hundreds of inmates from a prison in April.

The Yemeni security officials told CNN that the drone strike that killed al-Wuhayshi took place in southern Al Mukalla.

'This is a long, difficult struggle'

Yemen's descent into chaos prompted the United States to pull out its Special Operations forces based in the country in March, raising fears that its counterterrorism efforts against AQAP would be hobbled.

But al-Wuhayshi's death and an airstrike in April that killed a senior AQAP leader show that Yemen is no haven for the terrorist group.

U.S. Sen. Angus King, an independent from Maine, told CNN on Monday that the terrorist leader's death would hurt al Qaeda, but he stressed that the jihadist network still poses a threat.

"This is a long, difficult struggle that we're engaged in, and it's going to require all kinds of tools," he said.

News of al-Wuhayshi's death emerged days after U.S. planes carried out a strike inside Libya, purportedly killing a key terror figure in North Africa.

The target was Mokhtar Belmokhtar, a veteran Islamist fighter who is blind in one eye and affiliated with al Qaeda in North Africa, a U.S. official told CNN.

The Libyan government said Belmokhtar was killed in the weekend strike, something that U.S. officials have not confirmed.