When the time came to choose a college, Hill’s mother told the Fox Sports documentary Beyond the Glory, that she wanted him to attend Georgetown, while his father preferred the University of North Carolina. Hill decided to attend Duke University, playing four years with the Blue Devils and winning national titles in 1991 and 1992. Duke became the first Division I program to win consecutive titles since UCLA in 1966–73. Despite losing two of the biggest contributors on the Blue Devils, Christian Laettner (in 1992) and Bobby Hurley (each of whom went on to play in the NBA), Hill led Duke to the championship game once again in 1994, but lost to the Arkansas Razorbacks. Hill won the Henry Iba Corinthian Award as the nation’s top defensive player in 1993, and in 1994 he was the ACC Player of the Year. During his collegiate career, Hill became the first player in ACC history to collect more than 1,900 points, 700 rebounds, 400 assists, 200 steals, and 100 blocked shots. As a result of his successful college career, he became the eighth player in Duke history to have his jersey number (33) retired. After his freshman season at Duke, Hill played on the bronze medal-winning U.S. team at the 1991 Pan American Games, held in Havana, Cuba.

Hill also is widely known for his role in the Hail Mary play in the NCAA tournament regional final against Kentucky in 1992, which is considered by many to be one of the greatest college basketball games of all time. With Duke down 103–102 in overtime and 2.1 seconds remaining after Kentucky’s Sean Woods hit a floater, an unguarded Hill heaved the inbounds pass 75 feet across the court into the hands of Laettner, who dribbled once and spun before pulling up to make the game-winning jumper from just outside the free-throw line as time expired. Hill later produced a film, Duke 91 & 92: Back to Back about the team’s consecutive wins and this game-winning play.

Hill was drafted by the Detroit Pistons with the third pick in the NBA draft after graduating from Duke in 1994. He generally played the small forward position during his NBA career. In his first season, he averaged 19.9 points, 6.4 rebounds, 5.0 assists and 1.77 steals per game, and became the first Pistons rookie since Isiah Thomas in 1981–82 to score 1,000 points. Hill ended up sharing NBA Rookie of the Year Award honors with Jason Kidd of the Dallas Mavericks, becoming the first Piston since Dave Bing in 1966–67 to win the award. Hill also won the Sporting News Rookie of the Year Award. He was named to the all-NBA First Team in 1997, and All-NBA Second Teams in 1996, 1998, 1999, and 2000. Hill also regularly played in the NBA All-Star Game, where he made history by being the first rookie to lead an NBA All-Star fan balloting in (1994–95) with 1,289,585 votes, narrowly defeating Shaquille O’Neal. Also, he became the first rookie in any of the four major professional sports leagues to lead all-star fan voting.

Much like Scottie Pippen with the Bulls, Hill assumed the role of a “point forward” in Detroit, running the Pistons’ offense. As a result, between the 1995–96 and 1998–99 NBA seasons, Hill was the league leader in assists per game among non-guards all four seasons. In the lockout-shortened 1999 season, as he led his team in points, rebounds and assists for the third time, Hill joined Wilt Chamberlain and Elgin Baylor as the only players in NBA history to lead their teams in scoring, rebounding and assists more than once. Hill and Chamberlain are the only two players in league history to lead their teams in points, rebounds, and assists per game three times. Hill was selected to play in the 1998 FIBA World Championship, but in the end, no NBA players played in this tournament due to the lockout.

In Detroit, Michigan, Hill was introduced to Canadian singer Tamia by Anita Baker. Hill and Tamia married on July 24, 1999. Their daughter, Myla Grace Hill, was born on January 23, 2002. On August 9, 2007, Tamia gave birth to their second daughter, Lael Rose Hill. The family resides in Windermere, Florida.

In 1999–2000 season, Hill averaged 25.8 points while shooting 49% from the field, the season’s third-highest scoring average, behind MVP Shaquille O’Neal and Allen Iverson. He averaged 6.6 rebounds and 5.2 assists per game. However, despite Hill’s accomplishments in Detroit, the Pistons never made it far in the playoffs, either losing in the first round (1996, 1997 and 1999), or missing the playoffs entirely in the 1994–95 and 1997–98 seasons. The 2000 playoffs would be no different. On April 15, 2000, 7 days before the start of the playoffs, Hill sprained his left ankle in a game against the Philadelphia 76ers. He continued to play until the first-round playoff series against the Miami Heat, in which his injured ankle got worse, and Hill was forced to leave halfway through game 2. Eventually, the Heat swept the Pistons 3–0. Hill was initially selected for the 2000 Olympics U.S. team, but could not play due to the ankle injury. That ankle injury would prove to be a major liability for many years to come.

As an unrestricted free agent, Hill had planned to sign with the Orlando Magic. On August 3, 2000, however, a sign-and-trade deal allowed Hill to receive a slightly more lucrative contract while Detroit received at least some compensation for losing him. The Pistons signed Hill to a seven-year, $92.8 million contract and traded him to Orlando for Chucky Atkins and Ben Wallace. The Magic hoped he would team up with budding superstar Tracy McGrady, who had been signed away from the Toronto Raptors at that time, to return Orlando among the NBA elite. But Hill was hampered by ankle injuries, playing in only four games in his first season with the Magic, 14 games in his second and 29 in his third. He was forced to sit out his entire fourth year with Orlando (2003–04). Meanwhile, the Pistons, who had defeated the Magic in the 2003 Playoffs, but ended up losing to the New Jersey Nets in the Eastern Conference Finals, won the championship the following year in 2004.

In March 2003, Hill underwent a major surgical procedure in which doctors re-fractured his ankle and realigned it with his leg bone. Five days after the surgery was performed, Hill developed a 104.5 °F (40.3 °C) fever and convulsions and was rushed to a hospital. Doctors removed the splint around his ankle and discovered that Hill had contracted a potentially fatal methicillin-resistant Staphylococcus aureus (MRSA) infection. He was hospitalized for a week and had to take intravenous antibiotics for six months.

After contracting a life-threatening methicillin-resistant Staphylococcus aureus (MRSA) infection in 2003, Hill became an advocate for the awareness and prevention of MRSA and has appeared in public service announcements for Stop MRSA Now!, a non-profit organization.

Hill became an unrestricted free agent on July 1, 2007. On July 5 Hill’s agent, Lon Babby, said Hill intended to sign with the Phoenix Suns on July 11 (the first day free agents can officially sign contracts). Hill earned $1.83 million for 2007–08 with a $1.97 million player option for the next year. Hill was named captain along with Steve Nash. Hill was permitted by Suns Ring of Honor member, Alvan Adams, to wear his familiar No. 33 with the Suns. Hill adapted well to the Suns’ up-tempo style, averaging double figures in points as a key role player for Phoenix in the early months of the 2007–08 season. He played in the team’s first 34 games before an emergency appendectomy on January 9, 2008, sidelined him for two weeks. Despite being bothered by multiple injuries throughout the season, Hill had his first 70-game season since leaving Detroit, averaging 13.1 ppg, 5.0 rpg, and 2.9 apg in the process.

On July 10, 2009, the Associated Press reported that Hill decided to re-sign with the Phoenix Suns for a 2-year deal, despite an offer from the New York Knicks for the full mid-level exception and the Boston Celtics offering Hill the bi-annual exception. The first year of the contract is believed to be worth around $3 million with the second year at Hill’s option.

In 2010 the Phoenix Suns advanced to the Western Conference Semifinals, marking Hill’s first playoff series victory, and making him the first NBA player in history to win his first playoff series after 15 years in the league. After sweeping the San Antonio Spurs 4–0, the Suns then moved to the Western Conference Finals to face the Los Angeles Lakers, but lost in six games (4-2).

In 2010, he was chosen as the tenth-smartest athlete in sports by Sporting News.

On June 8 Hill exercised his option for the 2010–11 season. The Suns underwent two major roster changes in 2010–11. During the pre-season teammate Amar’e Stoudemire left for New York while Hedo Türkoğlu, Josh Childress and Hakim Warrick joined the Suns; within a year they also were traded for three other players. Hill became one of seven all-time NBA players to average 13 or more points at 38 years of age or older. On January 15, 2011, Hill passed the 16,000 career points milestone in a win over the Portland Trail Blazers.

On December 9, 2011, Hill decided to stay with the Phoenix Suns for one year, accepting a $6.5 million contract. By the end of the 2011–12 season, Hill had reached 17,000 career points, ending the season 78th on the all-time NBA scoring list (82nd NBA/ABA), 79th in career assists (83rd), and 66th in career steals (71st).

After his contract with the Suns expired, Hill was pursued by multiple contenders, including the Los Angeles Lakers, Miami Heat, New York Knicks, Portland Trail Blazers, and the Oklahoma City Thunder. On July 18, 2012, Hill signed a contract with the Clippers. Hill suffered a bruised bone in his right knee in the preseason which kept him out for three months. He then made his debut with the Clippers on January 12, 2013, against the Orlando Magic. During the 2012–13 season, he played only 29 games, averaging 3.2 ppg and 1.7 rpg in 15.1 mpg. The Clippers finished 56-26, fourth-best in the Western Conference, and won the Pacific Division for the first time in franchise history. However, the Clippers fell to the Memphis Grizzlies in a six-game series in the first round.

On June 1, 2013, Hill announced his retirement from professional basketball after 19 seasons in the NBA.

Beginning in 2013, Hill has hosted NBA Inside Stuff on NBA TV. He is also a sports broadcaster for CBS. In 2015, Hill was named to the lead announcing team for CBS and Turner Sports’ joint coverage of the NCAA Men’s Basketball Tournament, alongside March Madness stalwarts Jim Nantz and Bill Raftery.

On June 24, 2015, a deal was approved by the NBA Board of Governors to sell the Atlanta Hawks franchise for $850 million to a group led by Tony Ressler. Hill was a member of that group, and he thus became a co-owner of the team.

On September 7, 2018, Hill was inducted into the Naismith Basketball Hall of Fame.