He finished second in Indiana's "Mr. Basketball" voting that year behind Jared Jeffries, who played for the team the Giants beat in the state championship game and would later become Randolph's teammate with the Knicks.

After high school, Randolph attended and played basketball for Michigan State University coached by Tom Izzo.

Randolph averaged 23.6 points and 10.1 rebounds per game in the 2006–07 season, which was cut short in March 2007 due to a hand injury.

On November 21, 2008, after playing 11 games with the Knicks in the 2008–09 season, Randolph was traded to the Los Angeles Clippers along with Mardy Collins in exchange for Cuttino Mobley and Tim Thomas.

On May 15, 2013, Randolph helped lead the Grizzlies to victory over Oklahoma City to advance for the first time in franchise history to the Western Conference Finals.

On June 30, 2014, Randolph exercised his player option for the 2014–15 season and signed a two-year, $20 million contract extension with the Grizzlies.

[19][20] The Grizzlies advanced past Portland in the first round of the playoffs, but fell to eventual NBA champions, the Golden State Warriors, in the Conference Semifinals.

On March 19, 2016, Randolph recorded his first career triple-double with 28 points, 11 rebounds, and 10 assists in a 113–102 win over the Los Angeles Clippers.

On November 2, 2016, in a win over the New Orleans Pelicans, Randolph passed Pau Gasol (3,324) to become the Grizzlies' all-time leader in made field goals.

[22][23] On November 23, 2016, in a win over the Philadelphia 76ers, Randolph passed Vlade Divac for 46th on the NBA's all-time leading rebounding list.

[33] Randolph fell out of the rotation in 2018–19 due to the Kings' youth movement and the arrival of rookie Marvin Bagley III.

[34] He did not play for the team in his second season with the Kings and was later traded, along with Justin Jackson, to the Dallas Mavericks in exchange for Harrison Barnes on February 6, 2019.

[37] Randolph's final NBA game was played on March 19, 2018 in a 90 - 106 loss to the Detroit Pistons where he recorded 4 points, 3 assists and 2 rebounds as the Kings' starting Center.

[38] In a ceremony at FedExForum on December 11, 2021, Randolph's #50 jersey was retired by the Memphis Grizzlies, the team with which he enjoyed his greatest success.