Taylor played high school football in Pinecrest, a suburb of Miami. He originally began his high school football career at Miami Killian High School, a Class 2A public school, but transferred to Gulliver Preparatory School, a Class prep school, where he was a three-sport star in football, track and basketball. He played both offense and defense. Despite missing the first game of the season (the team’s only loss), he helped Gulliver win the Florida Class 2A State Championship in 2000 with a 14–1 record. Taylor was a star on both sides of the ball during that season, playing running back, defensive back and linebacker. He rushed for 1,400 yards and a state-record 44 touchdowns and on two separate occasions, rushed for more than 200 yards during Gulliver’s state playoff run. He also compiled more than 100 tackles during the season and scored three touchdowns (two receiving, one rushing) in the state title game victory over Marianna High School. In track & field, Taylor won the state 2A 100-meter dash in 2000 and was also one of the state’s top 400-meter dash sprinters. At Gulliver, Taylor was a teammate of future NFL player Buck Ortega. His championship HS team was coached by Steve Howey, Ralph Ortega, Dirk Moran, Lee Horn, Dave Burns, and John McCloskey.

As a freshman (one of four true freshmen to play for the team), Taylor carved a niche for himself in Miami’s secondary in nickel and dime defensive schemes. During the season, Taylor was named Big East Special Teams Player of the Week for his performance against the Pittsburgh Panthers. The Hurricanes won the national championship in 2001.

In 2002, his first season as a starter, Taylor was a second-team All-Big East selection by the league’s head coaches. He finished third on the team in tackles with 85 (53 solo), broke up 15 passes, intercepted 4 passes, forced one fumble, blocked one kick and returned a punt for a touchdown. He led all Miami defensive backs in tackles, interceptions and passes broken up, and had a career-high 11 tackles (2 solo) and intercepted 2 passes in the Fiesta Bowl loss to Ohio State. He made a critical play during the game, in which he intercepted Buckeyes quarterback Craig Krenzel in the endzone and returned the ball out of the endzone. Buckeyes running back Maurice Clarett ran Taylor down, and in the process stripped the ball away from him. Clarett recovered the ball for Ohio State, allowing them to kick a field goal to go up 17–7 at the time.

Following his 2003 season, Taylor announced that he was entering the NFL draft. He attended the NFL Scouting Combine in Indianapolis, Indiana, but opted to skip all of the combine drills and only met with team representatives and personnel.

On July 27, 2004, the Washington Redskins signed Taylor to a six-year, $18.5 million contract that includes a $13.4 million signing bonus and can be worth $40 million with incentives and bonuses. His contract also included a seventh-year option. Taylor became the first top ten pick to sign his contract in 2004.

On August 4, 2004, it was reported that Taylor fired his agents Eugene Mato and Jeff Moorad after he became unsatisfied with his contract. He fired them after other top ten picks signed their contracts and felt their deals were better in comparison. This marked his second time firing agents within five months after he fired agent Drew Rosenhaus two days after the NFL draft. He immediately rehired Rosenhaus, who served as his agent for the remainder of his career. Taylor also had an incident that involved his early departure during the NFL’s Rookie Symposium which was mandatory for every incoming player from the draft and was held over four days. He left after the first day, but returned for the last two days at the urgence of representatives from the Redskins. Over his first three seasons, Taylor also was fined at least seven times for late hits, uniform violations and other infractions.

Throughout training camp, Taylor competed for the job as the starting free safety against Andre Lott. On August 9, 2004, Taylor made his professional NFL debut in the Redskins’ preseason-opener as part of their second unit defense against the Denver Broncos. He recorded two interceptions in the second half off passes by rookie quarterback Matt Mauck. During the third quarter, Taylor intercepted a pass intended for Jeb Putzier and returned it for a three-yard touchdown to put Washington in the lead 10–9. Head coach Joe Gibbs named Taylor the backup free safety to begin the regular season, behind starter Andre Lott, after Taylor failed to surpass him on the depth chart.

He made his professional regular season debut in the Washington Redskins’ season-opener against the Tampa Bay Buccaneers and assisted on one tackle in their 16–10 victory. In Week 3, Taylor earned his first career start after surpassing Lott on the depth chart and recorded four combined tackles and deflected two passes in the Redskins’ 21–18 loss to the Dallas Cowboys. On October 18, 2004, Taylor made four solo tackles, a pass deflection, a sack, and returned his first career interception for 45-yards during a 13–10 win at the Chicago Bears. He made his first career interception and sack during the game, recording both on quarterback Brian Griese. In Week 12, he collected a season-high ten combined tackles (seven solo) and broke up a pass in a 16–7 loss at the Pittsburgh Steelers. He finished his rookie season in 2004 with 76 combined tackles (60 solo), nine pass deflections, four interceptions, two forced fumbles, and a sack in 15 games and 13 starts.

In October 2004, Taylor was arrested in Fairfax County, Virginia on a charge of driving under the influence of alcohol following a birthday party in Washington, D.C. for former Redskins receiver Rod Gardner. Pulled over for driving 82 mph on the Beltway, where the speed limit is 55 mph, Taylor failed a field sobriety test and then refused a blood alcohol (BAC) test, which resulted in his arrest. A Fairfax County judge acquitted Taylor of the charges in March 2005 after viewing a videotape of Taylor’s roadside sobriety tests that, according to the judge, failed to demonstrate obvious intoxication. Taylor was, however, convicted for refusing to take a blood alcohol test requested by a Virginia state police officer. But when this case was heard on appeal in March 2005, Taylor was acquitted of refusing to take the BAC test, with the judge ruling there was a lack of probable cause for the request.

Multiple players have honored Taylor by donning his jersey numbers that he wore during his college and professional career. During his college career Taylor wore No. 26 for the Miami Hurricanes. As a rookie in 2004, he wore No. 36 before switching to No. 21 for the remainder of his career. Taylor’s former teammate and fellow safety Ryan Clark returned to the Washington Redskins in 2014 after an eight-year stint with the Pittsburgh Steelers. During practices, Clark wore No. 21 in Taylor’s honor. The Washington Redskins’ second round pick in the 2016 NFL Draft, Su’a Cravens, chose No. 36 upon joining the Redskins as a rookie in dedication to Taylor. Cravens switched to No. 39 in 2017 after safety D. J. Swearinger requested No. 36 after signing with the Redskins as a free agent. Swearinger wore No. 36 throughout four teams in his professional career as a way to honor Taylor. On June 15, 2019, the New York Giants’ announced safety Landon Collins would switch from No. 27 to No. 21 to honor Taylor. Collins also wore Taylor’s college number (No. 26) during his collegiate career at Alabama as a way to pay tribute.

He started the Washington Redskins’ season-opener against the Chicago Bears and recorded four solo tackles and broke up a pass in their 9–7 victory. On November 11, 2005, it was reported that Taylor and teammate Clinton Portis received fines from the NFL due to violating the league’s uniform code during the Redskins’ 17–10 home victory against the Philadelphia Eagles in Week 9. Taylor’s fine was for $5,000 due to his choice of wearing white socks with a burgundy and gold striped pattern instead of the required all white socks. He was inactive for the Redskins’ Week 10 loss at the Tampa Bay Buccaneers due to an injury. On January 1, 2006, he collected a season-high nine combined tackles and deflected two passes during a 31–20 win at the Philadelphia Eagles. Taylor finished the 2005 season with 70 combined tackles (60 solo), a career-high ten pass deflections, two interceptions, two forced fumbles, and a sack in 15 games and 15 starts.

The Washington Redskins finished second in the NFC East with a 10–6 record and received a wildcard berth. On January 7, 2006, Taylor started in his first career playoff game and recorded seven combined tackles and returned a fumble recovery for a 51-yard touchdown in the first quarter of their 17–10 victory at the Tampa Bay Buccaneers. Referee Mike Carey ejected Taylor in the third quarter after he spit in Buccaneers’ running back Michael Pittman’s face. Defensive coordinator Gregg Williams stated Taylor denied the claim and he believed and stood by his player. During his rookie season, he allegedly spit in the face of wide receiver T. J. Houshmandzadeh, but was not reprehended due to the NFL being unable to recover clear video evidence. Two days later, the NFL fined Taylor $17,000 for the incident. The Redskins were eliminated the following game after losing 20-10 to the Seattle Seahawks in the NFC Divisional Round. Taylor finished the loss with seven combined tackles and a pass deflection.

Head coach Joe Gibbs named Taylor the starting free safety to start the regular season in 2006, along with starting strong safety Adam Archuleta.

On October 15, 2006, Taylor collected a season-high ten combined tackles (eight solo) and deflected a pass during a 25–22 loss to the Tennessee Titans. In Week 9, Taylor made eight combined tackles and returned a blocked 35-yard field goal attempt by Mike Vanderjagt for a 30-yard gain with less than six seconds left in the game. A facemask on Taylor by Kyle Kosier added a 15-yard penalty and placed the Redskins in field goal range with an untimed down. Vanderjagt’s game-winning field goal was blocked by Troy Vincent and allowed Redskins’ kicker Nick Novak to kick a 47-yard game-winning field goal to defeat the Dallas Cowboys 22–19. On November 26, 2006, Taylor recorded five combined tackles, two pass deflections, and intercepted a pass by quarterback Jake Delhomme in the Redskins’ 17–13 win against the Carolina Panthers. He made a key fourth down tackle on Jake Delhomme in the fourth quarter and his interception sealed the Redskins’ victory. He was voted as the NFC Defensive Player of the Week for his performance. He finished the 2006 season with a career-high 111 combined tackles (86 solo), six pass deflections, three forced fumbles, and an interception in 16 games and 16 starts. During the season, Washington Redskins assistant coach Gregg Williams frequently called Taylor the best athlete that he had ever coached.

In 2007, he was also named to the Florida High School Association All-Century Team, which selected the Top 33 players in the 100-year history of high school football in the state. After his death, Taylor was honored at Gulliver by a plaque that was placed in the school’s cafeteria. The football field at Gulliver Prep was renamed Sean Taylor Memorial Field on September 5, 2009.

Before the season started, Taylor switched his jersey number from No. 36 to No. 21 after it was available due to the departure of cornerback Fred Smoot to the Minnesota Vikings. Taylor kept the number when Smoot rejoined the Redskins in 2007, with Smoot opting to wear No. 27. Assistant head coach/defensive coordinator Gregg Williams opted to retain Taylor as the starting free safety to begin the regular season, alongside strong safety Ryan Clark.

On December 18, 2007, Taylor was posthumously voted to his second Pro Bowl, becoming the first deceased player in NFL history to be elected to the Pro Bowl. During the Pro Bowl, the Redskins players who had been selected, Chris Samuels, Chris Cooley and Ethan Albright, wore #21 to honor Taylor. Like the Redskins had done earlier in the season, the NFC lined up with just one safety on the first play of the game.

On November 18, 2007, burglars pried open a window to Taylor’s empty home and rifled through a desk and safe. On November 26, Taylor responded to hearing noises in his house and was shot in the upper leg by an intruder. His fiancée Jackie García and their 18-month-old daughter Jackie were not injured or killed. Taylor had extensive blood loss through a severed femoral artery and he died on the following day. Taylor’s funeral was held at the Pharmed Arena at Florida International University in Miami on December 3, 2007.

The first Redskins game after Taylor’s death was on December 2, 2007, which was against the Buffalo Bills and held at FedExField. The game began with the Redskins defense playing with 10 men on the field instead of the usual 11. Players signaled to the sky, holding up the numbers two and one, on numerous occasions. The team requested everyone arrive 25 minutes before the start of the game at 12:40pm and played a four-minute remembrance video, held a moment of silence and gave attendees commemorative towels with Taylor’s number on them in his honor and memory.

On November 30, four men – Venjah K. Hunte, 20; Eric Rivera, Jr., 17; Jason Scott Mitchell, 19; and Charles Kendrick Lee Wardlow, 18 – were arrested. Police said more than one confessed. All four men were charged with felony second-degree murder, armed burglary and home invasion robbery with a firearm, charges which carried a maximum of life in prison. In May 2008, a fifth suspect, 16-year-old Timothy Brown, was charged with first-degree murder and burglary. All the murder charges were subsequently increased to first-degree murder. The death penalty, however, was not sought because the gunman, Rivera, was 17 years old.

On May 12, 2008, it was announced the suspects, if convicted, would not face the death penalty, but may be subjected to life imprisonment because the suspected gunman, Eric Rivera, was only 17 at the time of the shooting. On May 15, 2008, Venjah Hunte, one of the five suspects in Taylor’s murder, accepted a plea deal and was sentenced to 29 years in prison. On April 1, 2009, Hunte petitioned the court to withdraw his guilty plea.

Taylor was inducted posthumously as the 43rd member into the Washington Redskins Ring of Fame on November 30, 2008.

Although originally scheduled for April 7, 2008, the trial of the men charged with Sean Taylor’s murder was postponed to June 2009. It was postponed by petition of the defense, saying that there were still hundreds of potential witnesses who needed to be interviewed before the trial could proceed. The trial was then delayed for a third time on June 9, 2009, for unspecified reasons. A new trial date was set for January 18, 2010, and was postponed again with a trial date of March 14, 2011. After another delay, the trial was set to begin on January 30, 2012.

On January 20, 2012, a judge set a trial date of April 16 for Eric Rivera, Jr., the alleged gunman in the case. However, Rivera fired his lawyer on March 16, eventually causing delays. On July 12, the judge postponed the trial to November 5, but that date was further moved back to April 5, 2013, due to a scheduling conflict with the chief prosecutor. On April 2, 2013, the trial was again postponed to August 12 of that year. Also in August, the trial was postponed to September 16 and later rescheduled to October 15. During his trial, Rivera testified that someone else fired the gun. On November 4, a jury found Eric Rivera, Jr. guilty of second-degree murder and armed burglary, which could carry a life imprisonment sentence.

On January 23, 2014, Miami-Dade Circuit Judge Dennis Murphy sentenced Rivera to 57⁄2 years in prison. On June 10, Jason Scott Mitchell was convicted in Taylor’s murder and sentenced to life imprisonment.

On April 1, 2015, Charles Wardlow, the fourth person charged with the death of Taylor, was sentenced to 30 years in prison. A week later, the final defendant, Timmy Lee Brown, was sentenced to 18 years in prison under his plea agreement.