In 1991, Sharpton founded the National Action Network, an organization designed to increase voter education, to provide services to those in poverty, and to support small community businesses.

The Crown Heights riot began on August 19, 1991, after a car driven by a Jewish man, and part of a procession led by an unmarked police car, went through an intersection and was struck by another vehicle causing it to veer onto the sidewalk where it accidentally struck and killed a seven-year-old Guyanese boy named Gavin Cato and severely injured his cousin Angela. Witnesses could not agree upon the speed and could not agree whether the light was yellow or red. One of the factors that sparked the riot was the arrival of a private ambulance which, on the orders of a police officer worried for the Jewish driver's safety, removed the uninjured driver from the scene while Cato lay pinned under his car. Cato and his cousin were treated soon after by a city ambulance. Caribbean-American and African-American residents of the neighborhood rioted for four consecutive days fueled by rumors that the private ambulance had refused to treat Cato. During the riot blacks looted stores, beat Jews in the street, and clashed with groups of Jews, hurling rocks and bottles at one another after Yankel Rosenbaum, a visiting student from Australia, was stabbed and killed by a member of a mob shouting "Kill the Jew." Sharpton marched through Crown Heights and in front of "770", shortly after the riot, with about 400 protesters (who chanted "Whose streets? Our streets!" and "No justice, no peace!"), in spite of Mayor David Dinkins's attempts to keep the march from happening.

In 1995, a black Pentecostal Church, the United House of Prayer, which owned a retail property on 125th Street, asked Fred Harari, a Jewish tenant who operated Freddie's Fashion Mart, to evict his longtime subtenant, a black-owned record store called The Record Shack. Sharpton led a protest in Harlem against the planned eviction of The Record Shack. Sharpton told the protesters, "We will not stand by and allow them to move this brother so that some white interloper can expand his business."

On December 8, 1995, Roland J. Smith Jr., one of the protesters, entered Harari's store with a gun and flammable liquid, shot several customers and set the store on fire. The gunman fatally shot himself, and seven store employees died of smoke inhalation. Fire Department officials discovered that the store's sprinkler had been shut down, in violation of the local fire code. Sharpton claimed that the perpetrator was an open critic of himself and his nonviolent tactics. Sharpton later expressed regret for making the racial remark, "white interloper," and denied responsibility for inflaming or provoking the violence.

In 1999, Sharpton led a protest to raise awareness about the death of Amadou Diallo, an immigrant from Guinea who was shot to death by NYPD officers. Sharpton claimed that Diallo's death was the result of police brutality and racial profiling. Diallo's family was later awarded $3 million in a wrongful death suit filed against the city.

In 2001, Sharpton was jailed for 90 days for protesting against U.S. military target practice exercises in Puerto Rico near a United States Navy bombing site. Sharpton, held in a Puerto Rican lockup for two days and then imprisoned at Metropolitan Detention Center, Brooklyn on May 25, 2001, has the Federal Bureau of Prisons ID# 21458-069. He was released on August 17, 2001.

In 2002, Sharpton was involved in protests following the death of West African immigrant Ousmane Zongo. Zongo, who was unarmed, was shot by an undercover police officer during a raid on a warehouse in the Chelsea neighborhood of Manhattan. Sharpton met with the family and also provided some legal services.

On November 25, 2006, Sean Bell was shot and killed in the Jamaica section of Queens in New York City by plainclothes detectives from the New York Police Department in a hail of 50 bullets. The incident sparked fierce criticism of the police from the public and drew comparisons to the 1999 killing of Amadou Diallo. Three of the five detectives involved in the shooting went to trial in 2008 on charges ranging from manslaughter to reckless endangerment but were found not guilty.

On May 7, 2008, in response to the acquittals of the officers, Sharpton co-ordinated peaceful protests at major transportation centers in New York City, including the Brooklyn Bridge, the Queensboro Bridge, the Triborough Bridge, the Manhattan Bridge, the Holland Tunnel, and the Queens-Midtown Tunnel. Sharpton and about 200 others were arrested.