During his time at Notre Dame, he was a two-time consensus All-American before declaring himself for the 2001 NBA draft, where he was selected by the Golden State Warriors with the 14th overall pick.

Murphy shared Big East Conference Player of the Year honors with Troy Bell of Boston College in 2001 and joined an elite group of four players—Chris Mullin (St. John's), Patrick Ewing (Georgetown) and Richard Hamilton (Connecticut)—as the only two-time winners of the award.

In addition to finishing fifth on the all-time career scoring list, upon his departure from the university, he ranked second in blocked shots (126), free throws made (587) and free throws attempted (755), sixth in rebounding and field goals made (680) and ninth in field goals attempted (1,370).

He realized this promise in his second pro season, averaging a double-double – 11.7 pts and 10.2 boards – and finishing second in Most Improved Player voting.

He spent the next offseason working extensively on his outside shooting; however, he never got much of a chance to test out his new jumper in 2003–04 after a series of injuries limited him to 28 games, with no starts.

With that part of his arsenal seemingly ready to go, Murphy spent the following offseason working on strength and conditioning as he looked to be a more well-rounded and complete player.

On January 17, 2007, Murphy was involved in an 8-player trade that sent him, Mike Dunleavy Jr., Ike Diogu, and Keith McLeod to the Indiana Pacers for Stephen Jackson, Al Harrington, Šarūnas Jasikevičius, and Josh Powell.

On February 23, 2011, the Warriors reacquired Murphy and a second round pick in exchange for Brandan Wright and Dan Gadzuric.

[citation needed] On November 2, 2012, Murphy signed with the Dallas Mavericks for the 2012–13 NBA season, replacing Eddy Curry.

[13] Murphy's final game in the NBA was played on November 28, 2012, in a 78 - 101 loss to the Chicago Bulls where he recorded 7 points, 2 rebounds and 2 blocks.