Medgar Evers was a native of Decatur, Mississippi, attending school there until being inducted into the U.S. Army in 1943. Despite fighting for his country as part of the Battle of Normandy, Evers soon found that his skin color gave him no freedom when he and five friends were forced away at gunpoint from voting in a local election. Despite his resentment over such treatment, Evers enrolled at Alcorn State University, majoring in business administration. While at the school, Evers stayed busy by competing on the school's football and track teams, also competing on the debate team, performing in the school choir and serving as president of the junior class.

He married classmate Myrlie Beasley on December 24, 1951, and completed work on his degree the following year. The couple moved to Mound Bayou, MS, where T.R.M. Howard had hired him to sell insurance for his Magnolia Mutual Life Insurance Company. Howard was also the president of the Regional Council of Negro Leadership (RCNL), a civil rights and pro self-help organization. Involvement in the RCNL gave Evers crucial training in activism. He helped to organize the RCNL's boycott of service stations that denied blacks use of their restrooms. The boycotters distributed bumper stickers with the slogan "Don't Buy Gas Where You Can't Use the Restroom." Along with his brother, Charles Evers, he also attended the RCNL's annual conferences in Mound Bayou between 1952 and 1954 which drew crowds of ten thousand or more.

Evers applied to the then-segregated University of Mississippi Law School in February 1954. When his application was rejected, Evers became the focus of an NAACP campaign to desegregate the school, a case aided by the U.S. Supreme Court ruling in the case of Brown v. Board of Education 347 US 483 that segregation was unconstitutional. In December of that year, Evers became the NAACP's first field officer in Mississippi.

After moving to Jackson, he was involved in a boycott campaign against white merchants and was instrumental in eventually desegregating the University of Mississippi when that institution was finally forced to enroll James Meredith in 1962.

In the weeks leading up to his death, Evers found himself the target of a number of threats. His public investigations into the murder of Emmett Till and his vocal support of Clyde Kennard left him vulnerable to attack. On May 28, 1963, a molotov cocktail was thrown into the carport of his home, and five days before his death, he was nearly run down by a car after he emerged from the Jackson NAACP office. Civil rights demonstrations accelerated in Jackson during the first week of June 1963. A local television station granted Evers time for a short speech, his first in Mississippi, where he outlined the goals of the Jackson movement. Following the speech, threats on Evers' life increased.

On June 12, 1963, Evers pulled into his driveway after returning from an integration meeting where he had conferred with NAACP lawyers. Emerging from his car and carrying NAACP T-shirts that stated, "Jim Crow Must Go", Evers was struck in the back with a bullet that ricocheted into his home. He staggered 30 feet before collapsing, dying at the local hospital 50 minutes later. Evers was murdered just hours after President John F. Kennedy's speech on national television in support of civil rights.

Mourned nationally, Evers was buried on June 19 in Arlington National Cemetery and received full military honors in front of a crowd of more than 3,000 people, the largest funeral at Arlington since John Foster Dulles. The past chairman of the American Veterans Committee, Mickey Levine, said at the services, "No soldier in this field has fought more courageously, more heroically than Medgar Evers."

On June 23, Byron De La Beckwith, a fertilizer salesman and member of the White Citizens' Council and Ku Klux Klan, was arrested for Evers' murder. During the course of his first 1964 trial, De La Beckwith was visited by former Mississippi governor Ross Barnett and one time Army Major General Edwin A. Walker.

All-white juries twice that year deadlocked on De La Beckwith's guilt, allowing him to escape justice. In response to the murder and miscarriage of justice, musician Bob Dylan wrote the song "Only a Pawn in Their Game" about Evers and his assassin. Phil Ochs wrote the songs "Too Many Martyrs" and "Another Country" in response to the killing (Evers is also mentioned in the song "Love Me I'm a Liberal"). Matthew Jones and the Student Nonviolent Coordinating Committee Freedom Singers paid tribute to Evers in the haunting "Ballad of Medgar Evers." Malvina Reynolds mentioned "the shot in Ever's back" in her song "It isn't nice".

Evers' legacy has been kept alive in a variety of ways. In 1970, Medgar Evers College was established in Brooklyn, NY as part of the City University of New York. In 1983, a made-for-television movie, For Us the Living: The Medgar Evers Story starring Howard Rollins, Jr. was aired, celebrating the life and career of Medgar Evers, and on June 28, 1992, he was immortalized in Jackson with a statue.

In 1994, thirty years after the two previous trials had failed to reach a verdict, Beckwith was again brought to trial based on new evidence concerning statements he made to others. During the trial, the body of Evers was exhumed from his grave for autopsy, and found to be in a surprisingly excellent state of preservation as a result of embalming. Beckwith was convicted on February 5, 1994, after living as a free man for three decades after the murder. Beckwith appealed unsuccessfully, and died in prison in January of 2001.

Before his body was reburied, owing to his excellent state of preservation, a new funeral was staged for Evers. This permitted his children, who were toddlers when he was assassinated and had very little memory of him, to have a chance to see him. The new funeral was covered on HBO's Autopsy series.

The 1996 film Ghosts of Mississippi tells the story of the 1994 trial, in which a District Attorney's office prosecutor, Robert Delaughter, successfully retried the case, and won.

Evers's wife, Myrlie, became a noted activist in her own right later in life, eventually serving as chairwoman of the NAACP. Medgar's brother Charles returned to Jackson in July 1963 and served briefly in his slain brother's place. Charles Evers remained involved in Mississippi Civil Rights for years to come. He resides in Jackson.

In 2001, Myrlie and Medgar's oldest son, Darrell Kenyatta Evers, died of colon cancer. Their two surviving children are Reena Denise and James Van.