The West starting five is Kobe Bryant and Dwight Howard of the Lakers, Oklahoma City's Kevin Durant, and Clippers teammates Chris Paul and Blake Griffin.
The Clippers were hoping for a third All-Star, but sixth-man Jamal Crawford wasn't picked.
Commissioner David Stern would choose the replacement if any players are injured.
Randolph leads the NBA with 27 double-doubles and becomes the first Grizzlies player with multiple selections.
"It is truly an honor to be named by the NBA's coaches to the 2013 Western Conference All-Star team," he said in a statement. "I am grateful for this opportunity and look forward to playing with the best players in the world."
The leaders of the teams with the best winning percentage in their conference through games of Feb. 3 will be the coaches. Miami's Erik Spoelstra has the inside track on the East spot, while San Antonio's Gregg Popovich and the Clippers' Vinny Del Negro are battling for the West honor since Scott Brooks, whose Thunder have the league's best record, is ineligible after coaching last year.
Irving, the reigning Rookie of the Year, and Holiday were rewarded for outstanding individual seasons even though their teams are well below .500. Irving is the Cavaliers' first All-Star since James, the only other East player averaging at least 20 points and five assists.
"It's one of the best days of my life," Irving said Thursday night, shortly after also being honored as Cleveland's professional athlete of the year award at the Greater Cleveland Sports Awards. "It's a big deal for me and it's a big deal for the city of Cleveland to be picked as an All-Star for the first time. I'm turning 21 on March 23 and to be with those guys, to see those names on TV, that was truly a blessing."
The 22-year-old Holiday, the youngest All-Star in franchise history, is averaging 19.0 points and 9.0 assists but feared the 76ers' 17-25 mark would work against him.
"I thought so. I definitely thought so. I think anybody else probably would, too," he said while watching a Philadelphia Flyers game. "We're not getting on a winning streak or anything like that. I just tried to stay positive and not talk about it."
AP Sports Writers Dan Gelston in Philadelphia, Antonio Gonzalez in Oakland, Calif., and Tom Withers in Cleveland contributed to this report.