Haslem was born in Miami, Florida. He attended Wolfson High School in Jacksonville, Florida, then Miami Senior High School in Miami. He helped lead Miami High to state titles in 1997 and 1998 (the last of three in a row), playing alongside another future NBA player, Steve Blake. The team was coached by current South Carolina head coach Frank Martin.
However, an investigation by the Miami New Times revealed that Haslem, Blake and several other players circumvented residency requirements. The New Times reported that while he claimed to live in Miami, he actually lived in Miramar, in Broward County. His official school address was an efficiency apartment owned by a longtime Miami High booster, which was also a violation of Florida High School Athletic Association (FHSAA) rules. As a result, Miami High was stripped of its 1998 title and ordered to forfeit its entire schedule.
Haslem accepted an athletic scholarship to attend the University of Florida in Gainesville, Florida, where he played for coach Billy Donovan's Florida Gators basketball team from 1998 to 2002, while majoring in leisure service management. As the Gators' starting center for four years, he was part of Donovan's 1998 recruiting class that raised the national prominence of the Florida Gators basketball program, and included future Miami Heat teammate Mike Miller. Fans would yell the letter "U" in unison after his big plays. His sophomore season saw the team advance to the NCAA Men's Division I Basketball Championship game, before falling to the Michigan State Spartans. The Gators received NCAA tournament invitations all four years he was with the team–the first time in the program's history. Haslem ranks third in school history in points scored (1,782) and tenth in rebounds (831). He was inducted into the University of Florida Athletic Hall of Fame as a "Gator Great" in 2012.
After leaving Florida in 2002, his weight ballooned in excess of 300 pounds and he became a late-preseason roster cut with the Atlanta Hawks. Haslem then signed with Chalon-Sur-Saône, a professional team in France. While averaging 16.1 points and 9.4 rebounds per game, Haslem also managed to lose 70 pounds over the course of that year, which resulted in his earning a spot in the NBA summer leagues.
He was signed by the Miami Heat as an undrafted rookie in 2003. As a rookie, he backed up Brian Grant and provided rebounding and defense. He was named to the NBA All-Rookie Second Team, and played in the rookie challenge during All-Star weekend. He assumed the starting power forward position in 2004 after teammate Lamar Odom was traded as part of a package that was shipped to the Los Angeles Lakers in a deal that brought superstar center Shaquille O'Neal back to Florida. He was helpful yet again, being a tough rebounder and developing an effective 15 foot jump-shot. He has been called a perfect complement to O'Neal's style of play, and was critical in the Heat's playoff run to the Eastern Conference Finals against the Detroit Pistons. Following the season his two-year contract was renewed after upping his rookie averages of 7.3 points and 6.3 rebounds to 10.9 and 9.1 in his second season. In 2005–2006, he again was the starting power forward. Despite increased pressure from O'Neal battling injuries and the acquisition of three-time All-Star Antoine Walker, Haslem retained the starting spot.
On April 22, 2006, in a first-round playoff game against the Chicago Bulls, Haslem was ejected for throwing his mouthpiece at referee Joe Crawford. Haslem had been upset that a foul was not called on a play on the Bulls' end of the court. After the game, he claimed that he had not deliberately aimed at Crawford, and that the mouthpiece's trajectory was an accident. He apologized to fans and to his teammates, and stated that he would also apologize to Crawford when the opportunity arose. The NBA reviewed the incident, and they suspended Haslem for game 2 of the series against the Bulls on April 24, 2006.
Haslem started every playoff game as the Heat defeated the Bulls, Nets and Pistons before reaching the Finals against the Dallas Mavericks. He scored 17 points in the title-clinching game 6.
On November 10, 2006, Haslem scored a career-high 28 points on 10-for-14 shooting and grabbed nine rebounds in a 113–106 win over the Nets. He would continue to start at power forward in the 2006-2007 regular season. In the 2007-2008 season with Shaquille O'Neal having been traded and Alonzo Mourning going down with an injury, Haslem played the center position and averaged 12 points and 9 rebounds.
In the 2008-2009 season, Haslem started at power forward as the Heat reached the playoffs before falling in 7 games to the Atlanta Hawks. The following season, Haslem came off the bench with Quentin Richardson filling in the small forward position and Michael Beasley being named the starting power forward.
Following the Heat's acquisition of LeBron James and Chris Bosh and the re-signing of Dwyane Wade, there was speculation as to whether Haslem would remain with the team or sign elsewhere. On July 12, 2010, Haslem re-signed with the Heat, even though he would have received nearly $10 million more if he were to sign with the Dallas Mavericks or Denver Nuggets. 13 games into the season, Haslem would be sidelined by a torn ligament in his foot. He would return in during the playoffs against the Boston Celtics and had a breakout performance in game 2 of the Eastern Conference Finals against the Chicago Bulls, scoring 13 points in 23 minutes. The Heat would advance to the Finals but would lose in 6 games to the Dallas Mavericks.
In the 2011–12 season Haslem averaged 6 points and 7.3 rebounds in 64 games backing up Chris Bosh. He would play extended minutes when Bosh was hurt during the East semifinals against the Indiana Pacers, and posted double figure scoring games in games 4 and 5. He would be suspended for game 6 following a flagrant foul in the previous game. After defeating Indiana and then defeating the Boston Celtics in 7 games, the franchise would win its second championship against the Oklahoma City Thunder with Haslem and Wade being the only remaining players from the 2006 championship team. Haslem averaged 4.8 points and 6.4 rebounds in the 2012 playoffs.
In the 2012–13 season, Haslem continued to come off bench for the Heat. On November 21, 2012 in a game against the Milwaukee Bucks, Haslem passed Alonzo Mourning to become the franchise leader in total rebounds with 4,808, breaking Mourning's previous record of 4,807. Mourning was in attendance for the game and applauded Haslem for his milestone. Haslem also became the first undrafted player to lead a franchise in rebounding. During the 2012-13 regular season, Haslem averaged a career-low 18.9 minutes, but his shooting percentage from the field (51%) returned to just over his career-average level after dropping to 42% the previous season. In the 2013 playoffs, Haslem shot 8-9 from the field in both Game 3 and Game 5 of the Eastern Conference Finals against the Indiana Pacers. He won his third championship on June 20, 2013, when the Heat defeated the San Antonio Spurs in an intense seven game series.