On April 21, 2025, Pope Francis passed away due to a stroke and heart failure. Public prayers were held in Vatican's Saint-Pierre square, and Catholics worldwide, including in the UK, India, Ireland, Israel, Syria, Nigeria, and the New York Stock Exchange, gathered in remembrance. Global political and religious leaders, including Emmanuel Macron, Donald Trump, Ursula von der Leyen, the Dalai Lama, and the rector of the Grand Mosque of Paris, offered tributes.

On April 21, 2025, President Zelenskyy sought a response from Russia regarding his proposal for a 30-day truce on attacks against civilian infrastructure, extending the "Easter truce". Vladimir Putin stated Russia would analyze the offer and mentioned the possibility of bilateral consultations, which would be a first since the spring of 2022.

On April 21, 2025, Ronen Bar, the former head of the Shin Bet, accused Israeli Prime Minister Benjamin Netanyahu in a sworn statement to the Supreme Court. Netanyahu’s office dismissed the statements as false, stating that Mr. Bar had "failed miserably" on October 7.

On April 21, 2025, Mike Huckabee, the US ambassador to Israel, called on Hamas to conclude an agreement guaranteeing the release of hostages held in Gaza in exchange for humanitarian aid, which has been suspended since March 2.

On April 21, 2025, it was reported that the US sees India as a strategic ally against China's influence in the Asia Pacific region. Modi and Trump announced plans to expand their defense partnership, with India agreeing to purchase more US oil, energy, and defense equipment.

On April 21, 2025, UN Humanitarian Chief Tom Fletcher spoke with SAF General al-Burhan and RSF General Abdelrahim Dagalo, who committed to providing aid access. The UN described the situation as "horrifying" and warned of a catastrophic humanitarian situation, with aid access remaining dangerously restricted.

On April 21, 2025, it was reported that on April 20, 2025, the WHO warned that the freezing of US foreign aid by President Donald Trump is worsening the health situation in conflict zones, particularly in Gaza and Sudan.

On April 21, 2025, Harvard University sued the Trump administration over the freezing of $2.2 billion in grants. Harvard's lawsuit argues the government's actions violate the First Amendment and federal laws.

On April 21, 2025, Israeli Finance Minister Bezalel Smotrich stated that « The return of the hostages is not the most important objective ». The Forum of Hostage and Missing Families reacted strongly, stating « The families have only one word this morning: “Shame”. »

On April 21, 2025, the Israeli army affirmed to have killed a member of the Palestinian Islamic Jihad who participated in the October 7 attacks.

On April 21, 2025, the Houthi rebel group reported that at least 12 people were killed in fresh US air strikes on Yemen's capital, confirming earlier reports from April 20, 2025.

On April 21, 2025, according to the Palestinian news agency WAFA, Israeli bombardments caused 17 deaths and dozens of injuries in the Gaza Strip.

On April 21, 2025, Iran announced that Foreign Minister Abbas Araghchi would visit China to brief them before a third round of nuclear program talks with the US. The third round of talks with US envoy Steve Witkoff is scheduled for Saturday in Oman.

On April 21, 2025, Al Jazeera published a video about the US military increasing its presence in Japan, Guam, and Hawaii due to rising tensions with China over Taiwan, exploring the effects on local communities.

On April 21, 2025, President Trump announced sweeping tariffs, including 26 percent levies on India, but later paused these tariffs for 90 days to leverage better trade deals with partners like India.

On April 21, 2025, US Vice President JD Vance arrived in India for a four-day visit to strengthen ties and negotiate a bilateral trade deal. Vance met with Prime Minister Narendra Modi to discuss strengthened bilateral ties, with India's Ministry of External Affairs stating that Vance’s visit would further deepen the India-US comprehensive global strategic partnership.

On April 20, 2025, at least three blasts were reported in the Russian-controlled Donetsk region during an Easter ceasefire. Ukraine and Russia accused each other of violating the ceasefire, while a Ukrainian soldier was seen using a BM-21 Grad rocket launcher near Pokrovsk, Ukraine.

On April 20, 2025, the RSF and allied militias attacked el-Fasher, resulting in over 30 deaths and numerous injuries due to heavy artillery shelling.

On April 21, 2025, the UN warned that Asian scam operations worth €35 billion are spreading across the world.

On April 21, 2025, Russian journalist Ekaterina Barabach, under house arrest for spreading "false information" about the Russian army, is presumed to have fled and is now on a wanted list. She faces up to ten years in prison if convicted.

On April 21, 2025, US Representatives visited El Salvador to advocate for the release of Kilmar Abrego Garcia, who was expelled from the US in mid-March 2025 due to an administrative error.

Reported on April 21, 2025, starting mid-May 2025, residents of Western Sahara can apply for visas to France from Laayoune and Dakhla, where 60% of the population is concentrated.