Operation Infinite Reach was the codename for American cruise missile strikes on al-Qaeda bases that were launched concurrently across two continents on 20 August 1998. Launched by the U.S. Navy, the strikes hit the al-Shifa pharmaceutical factory in Khartoum, Sudan, and a camp in Khost Province, Afghanistan, in retaliation for al-Qaeda's August 7 bombings of American embassies in Kenya and Tanzania, which killed 224 people (including 12 Americans) and injured over 4,000 others. Operation Infinite Reach was the first time the United States acknowledged a preemptive strike against a violent non-state actor.

U.S. intelligence wrongly suggested financial ties between the al-Shifa plant, which produced over half of Sudan's pharmaceuticals, and Osama bin Laden; a soil sample collected from al-Shifa allegedly contained a chemical used in VX nerve gas manufacturing. Suspecting that al-Shifa was linked to, and producing chemical weapons for, bin Laden and his al-Qaeda network, the U.S. destroyed the facility with cruise missiles, killing or wounding 11 Sudanese. The strike on al-Shifa proved controversial; after the attacks, the U.S. evidence and rationale were criticized as faulty, and academics Max Taylor and Mohamed Elbushra cite "a broad acceptance that this plant was not involved in the production of any chemical weapons."

The missile strikes on al-Qaeda's Afghan training camps were aimed at preempting more attacks and killing bin Laden. These strikes damaged the installations, but bin Laden was not present at the time. Two of the targeted camps were run by the Inter-Services Intelligence of Pakistan, which at the time was allied to the US, who were training militants to fight in Kashmir; in all, five ISI officers were confirmed killed and at least twenty militants also died. Following the attacks, Afghanistan's ruling Taliban allegedly reneged on a promise to Saudi intelligence chief Turki bin Faisal to hand over bin Laden, and the regime instead allegedly strengthened its ties with the al-Qaeda chief.

Operation Infinite Reach, the largest U.S. action in response to a terrorist attack since the 1986 bombing of Libya, was met with a mixed international response: U.S. allies and most of the American public supported the strikes, but many across the Muslim world disapproved them, viewing them as attacks specifically against Muslims, a factor that was further capitalized by radicals. The failure of the attacks to kill bin Laden also enhanced his public image in parts of the Muslim world. Further strikes were planned but not executed; as a 2002 congressional inquiry noted, Operation Infinite Reach was "the only instance ... in which the CIA or U.S. military carried out an operation directly against Bin Laden before September 11."

On 23 February 1998, Osama bin Laden, Ayman al-Zawahiri, and three other leaders of Islamic militant organizations issued a fatwa in the name of the World Islamic Front for Jihad Against Jews and Crusaders, publishing it in al-Quds al-Arabi. Deploring the stationing of U.S. troops in Saudi Arabia, the sanctions against Iraq, and U.S. support for Israel, they declared that "The ruling to kill the Americans and their allies—civilian and military—is an individual duty for every Muslim who can do it in any country in which it is possible to do it." In spring 1998, Saudi elites became concerned about the threat posed by al-Qaeda and bin Laden; militants attempted to infiltrate surface-to-air missiles inside the kingdom, an al-Qaeda defector alleged that Saudis were bankrolling bin Laden, and bin Laden himself lambasted the Saudi royal family. In June 1998, Al Mukhabarat Al A'amah (Saudi intelligence) director Prince Turki bin Faisal Al Saud traveled to Tarnak Farms to meet with Taliban leader Mullah Omar to discuss the question of bin Laden. Turki demanded that the Taliban either expel bin Laden from Afghanistan or hand him over to the Saudis, insisting that removing bin Laden was the price of cordial relations with the Kingdom. American analysts believed Turki offered a large amount of financial aid to resolve the dispute over bin Laden. Omar agreed to the deal, and the Saudis sent the Taliban 400 pickup trucks and funding, enabling the Taliban to retake Mazar-i-Sharif. While the Taliban sent a delegation to Saudi Arabia in July for further discussions, the negotiations stalled by August.

Around the same time, the U.S. was planning its own actions against bin Laden. Michael Scheuer, chief of the Central Intelligence Agency's bin Laden unit (Alec Station), considered using local Afghans to kidnap bin Laden, then exfiltrate him from Afghanistan in a modified Lockheed C-130 Hercules. Documents recovered from Wadih el-Hage's Nairobi computer suggested a link between bin Laden and the deaths of U.S. troops in Somalia. These were used as the foundation for the June 1998 New York indictment of bin Laden, although the charges were later dropped. The planned raid was cancelled in May after internecine disputes between officials at the FBI and the CIA; the hesitation of the National Security Council (NSC) to approve the plan; concerns over the raid's chance of success, and the potential for civilian casualties.

Al-Qaeda had begun reconnoitering Nairobi for potential targets in December 1993, using a team led by Ali Mohamed. In January 1994, bin Laden was personally presented with the team's surveillance reports, and he and his senior advisers began to develop a plan to attack the American embassy there. From February to June 1998, al-Qaeda prepared to launch their attacks, renting residences, building their bombs, and acquiring trucks; meanwhile, bin Laden continued his public-relations efforts, giving interviews with ABC News and Pakistani journalists. While U.S. authorities had investigated al-Qaeda activities in Nairobi, they had not detected any warnings of imminent attacks.

On August 7, 1998, al-Qaeda teams in Nairobi, Kenya, and Dar es Salaam, Tanzania, attacked the cities' U.S. embassies simultaneously with truck bombs. In Nairobi, the explosion collapsed the nearby Ufundi Building and destroyed the embassy, killing 213 people, including 12 Americans; another 4,000 people were wounded. In Dar es Salaam, the bomber was unable to get close enough to the embassy to demolish it, but the blast killed 11 Africans and wounded 85. Bin Laden justified the high-casualty attacks, the largest against the U.S. since the 1983 Beirut barracks bombings, by claiming they were in retaliation for the deployment of U.S. troops in Somalia; he also alleged that the embassies had devised the Rwandan genocide as well as a supposed plan to partition Sudan.