On 2025-04-21, US stock markets fell after Donald Trump criticized Federal Reserve chair Jerome Powell. The Dow fell 2.5%, Nasdaq Composite fell over 2.5%, and S&P 500 fell 2.4%. Trump has also floated terminating Powell, whose term ends in May 2026, and the administration is studying the legality of firing him. The Fed, which aims for a 2% inflation rate, will meet May 6-7 to discuss interest rate changes, after inflation cooled to 2.4% last month.

On April 21, 2025, Harvard University announced it was suing the Trump administration to halt a freeze on more than $2.2 billion in grants. Harvard stated it would defy the administration’s demands to limit activism on campus, leading to the government freezing billions in federal funding, according to the Los Angeles Times.

On April 21, 2025, the Education Department announced that student loans in default would be referred to debt collection starting next month. This ends the COVID-19 pandemic leniency period that began in March 2020.

On April 21, 2025, China announced sanctions against U.S. officials, lawmakers, and NGO leaders for their stance on Hong Kong issues, following U.S. sanctions in March against six Chinese and Hong Kong officials.

On 2025-04-21, it was reported that the Trump administration rejected plans to reduce lanes on highways to prevent accidents. The administration argued that reducing lane capacity could lead to more crashes and erratic maneuvers.

On April 21, 2025, the US Supreme Court heard arguments regarding the constitutionality of the US preventive services taskforce. Two Christian businesses and some Texas residents sued the federal government, objecting to the task force’s approval of no-cost H.I.V. medications, claiming the drugs "encourage and facilitate homosexual behavior."

On 2025-04-21, a nonprofit watchdog group broadened a lawsuit against top national security officials in the Trump administration. The lawsuit asks a federal judge to force them to preserve all messages sent on Signal, an encrypted communications app, as part of their official business.

President Donald Trump criticized the Supreme Court's ruling temporarily halting deportations under the Alien Enemies Act, saying "we cannot give everyone a trial."

On 2025-04-21, Walgreens agreed to pay up to $350 million in a settlement with the U.S. Justice Department after allegations that the pharmacy chain illegally filled millions of invalid prescriptions for opioids and other controlled substances.

On April 21, 2025, American politicians and religious leaders, including the White House, Donald Trump, Joe Biden, Marco Rubio, Barack Obama, Hillary Clinton, Hakeem Jeffries, and Amy Klobuchar, reacted to the death of Pope Francis with expressions of mourning and tributes.

On April 21, 2025, U.S. Vice President JD Vance met with Modi in New Delhi as India sought reprieve from Trump tariffs.

On 2025-04-21, reports indicated that the Trump administration's cuts to a sexually transmitted infection lab at the Centers for Disease Control and Prevention (CDC) occurred amidst a dramatic rise in syphilis cases in the US. However, a 2023 CDC report indicated that new HIV infections in the US decreased by 12% between 2018 and 2022 due to new government supports.

On 2025-04-21, Los Angeles Mayor Karen Bass delivered her State of the City address, acknowledging the city's challenges, including a significant budget shortfall and the need to rebuild after the Palisades fire. She presented a budget proposal that includes layoffs of approximately 1,650 city employees.

On April 21, 2025, four Democratic members of Congress visited El Salvador to advocate for the return of Kilmar Abrego Garcia, a wrongly deported U.S. citizen, but were denied a meeting with him by the Salvadoran government. Representatives Robert Garcia, Maxwell Alejandro Frost, Yassamin Ansari, and Maxine E. Dexter met with U.S. Ambassador William H. Duncan and urged him to raise the issue with Salvadoran officials, and a U.S. Embassy official stated that the concerns of the lawmakers had been relayed to the Salvadoran government regarding Kilmar Armando Abrego Garcia and Andry Jose Hernandez Romero.

On 2025-04-21, it was reported that US businesses reliant on Chinese products are facing significant challenges due to recent tariff rate hikes. Restaurants, online markets, and importers are experiencing price increases on imported goods.

On 2025-04-21, it was reported that Trump aides are exploring ideas to increase the birthrate, including potential baby bonuses and fertility planning initiatives. The White House birthrate boosters see an ally in Elon Musk.