The second of four children, McGinest attended Long Beach Polytechnic High School, where he garnered all-state honors in football and basketball. In football, he earned All-American recognition from Super Prep, Blue Chip and Tom Lemming magazines and was selected to several all-star teams, earning all-city, all-state, and all-region honors as a linebacker in 1989. He totaled 107 tackles, including 18 sacks, two fumble recoveries, four passes defensed, including an interception, and blocked four kicks as a senior. In 2009, McGinest was elected to Poly’s Football Hall of Fame. On the court, he earned Long Beach Press-Telegram “Best in the West,” All-CIF Southern Section and all-league honors while averaging 14 points per game during the 1989-90 season.

From 1990 to 1993, McGinest played football at the University of Southern California. He wore number 55. McGinest earned all-conference honors three straight years and All-American acclaim. During his senior year, he was a Lombardi Award finalist, and earned All-American and All-Pac-10 conference honors. He started every game at weakside defensive end for the Trojans. McGinest finished his collegiate career with 193 tackles (134 solos), 29 sacks (171 yards), 48 tackles for loss (238 yards), and 26 passes batted away. McGinest received a degree in public administration from USC in 1994.

Assault trial McGinest and teammates Michael Jones and Jason Oliver were charged with battery and false imprisonment when a female USC student accused them of sexual assault on October 15, 1990. The incident in question occurred on June 20 of the same year. The 23-year-old summer school counselor said she was dragged into a dormitory room, pinned to a bed and sexually molested. The players contend the woman entered the room voluntarily and was involved in “horseplay.” Key witnesses told prosecutors that Valerie Paton, a USC assistant dean of student affairs, sent a memo to campus security that asked officers to pull the file on the incident so that it would not become public in an effort to save the players. USC Security Guard Morris DeMayo was abruptly fired with Valerie Paton for their roles in an alleged cover-up when the players were charged. On June 15, 1991 the three players including McGinest were acquitted of all sexual assault and false imprisonment charges.

McGinest was drafted by the New England Patriots in the first round (fourth overall) of the 1994 NFL Draft. He was one of the cornerstones for New England’s success in winning the Super Bowl in 2001, 2003, and 2004. He was named to the Pro Bowl twice, in 1996 and 2003. In Super Bowl XXXIX, McGinest was used in a different manner from his regular role. While he usually lined up as an outside linebacker in a 3-4 scheme, the Patriots moved him to the defensive line as a defensive end in an effort to keep Philadelphia quarterback Donovan McNabb from scrambling.

In a 2005 wild card playoff win over the Jacksonville Jaguars, McGinest eclipsed two NFL postseason records—most sacks in a game (4.5) and most career postseason sacks (16), surpassing Bruce Smith. His 78 career sacks rank third all time for the Patriots.

McGinest established the Willie McGinest Freedom School, a program which aims to provide social and cultural enrichment for neighborhood youth. On May 3, 2005, the city council of Long Beach declared that every year, May 3 will be recognized as Willie McGinest Day in recognition of his charitable efforts and civic involvement. During the 2004 holiday season, McGinest sponsored “Shop with a Jock,” an event that gave 50 Boston-area children the opportunity to go on a $100 shopping spree with him and his teammates. He would go on to sponsor a similar event in the Cleveland area with Browns teammates.

On March 15, 2006, McGinest signed with the Cleveland Browns, reuniting with head coach Romeo Crennel, who was the Patriots’ defensive coordinator during McGinest’s stint in New England. McGinest signed a three-year deal worth $12 million with $6 million in guarantees and bonuses. He stated in an interview prior to the 2008 season that he would be playing his final year of professional football before retiring in the offseason. In July 2009, he stated that he would like to end his career with the Patriots. On August 5, 2015, he signed a one-day contract with the Patriots during his Patriots Hall of Fame induction ceremony.

McGinest was featured on the NFL Network’s documentary series A Football Life on October 5, 2018.