DeRozan, who missed the Raptors last two games with a sprained ankle, leads the team in scoring with 21.8 points per game.
This will be his third appearance at the NBA All-Star weekend — he participated in the Slam Dunk competition in 2010 and 2011, and also suited up for the 2011 Rookie Challenge — but this year's event will mark his first time in the actual game.
The Portland Trail Blazers and Houston Rockets each had two players picked as reserves, while the Indiana Pacers had to settle for just Roy Hibbert despite the league's best record.
LaMarcus Aldridge and Damian Lillard made it from the Trail Blazers, who have been among the Western Conference leaders all season.
Dwight Howard, who was passed late in fan voting for a starting spot, was chosen Thursday along with Houston teammate James Harden.
Old reliables Chris Paul, Tony Parker and Dirk Nowitzki round out the West reserves for the Feb. 16 game in New Orleans.
Nowitzki earned his 12th selection, tying him for sixth all-time with nine players.
"I have been a part of All-Star weekend every year since I have been in the league and not being there last year felt strange," Nowitzki said in a statement. "The Dallas fan base has always been great to me and the Mavericks' organization and the city deserves to be represented at the All-Star game."
The rest of the East reserves are: Miami's Chris Bosh, Washington's John Wall, Brooklyn's Joe Johnson, Chicago's Joakim Noah and Atlanta's Paul Millsap.
Wall is the first Wizards All-Star since Caron Butler and Antawn Jamison were picked in 2008, the last time the game was in New Orleans.
"I am very proud to represent the Wizards franchise and the city of Washington as an All-Star and to share this honour with the fans who have supported me and stuck by me since I arrived here," said Wall, the No. 1 pick in the 2010 draft.
The Pacers hoped Lance Stephenson, who leads the NBA in triple-doubles, would also be selected to join Hibbert and Paul George, who was voted to start.
The reserves were chosen by the coaches from each conference, who had to vote for two guards, three frontcourt players and two regardless of position. They were not allowed to vote for their own players.
The West ones went for veterans with their choices at guard in Paul, last year's All-Star game MVP from the Los Angeles Clippers, and the Spurs' Parker. That left first-time hopefuls Goran Dragic of Phoenix and Mike Conley Jr. of Memphis home.
The starters were announced last week: Miami's LeBron James and Dwyane Wade, New York's Carmelo Anthony and Cleveland's Kyrie Irving were voted to start along with George.
The fans voted for NBA scoring leader Kevin Durant of Oklahoma City, the Lakers' Kobe Bryant, Golden State's Stephen Curry, Minnesota's Kevin Love and the Clippers' Blake Griffin.
Bryant is injured and not expected to play. Adam Silver, who will become commissioner Saturday, will choose replacements for Bryant and any other injured players.
Indiana's Frank Vogel and Oklahoma City's Scott Brooks will coach the game. Brooks would determine who replaces Bryant in the starting lineup.
Bosh is an All-Star for the ninth time in 11 seasons, while Lillard, Wall, DeRozan and Millsap were all chosen for their first All-Star game. Millsap was the Eastern Conference player of the week last week.
"Paul has been an All-Star player and an All-Star teammate for us," general manager Danny Ferry said. "The Atlanta Hawks are very proud to have Paul representing the city of Atlanta and our team."
Hometown hopeful Anthony Davis of the Pelicans, and centres DeAndre Jordan of the Clippers and DeMarcus Cousins of Sacramento were among those who missed out. Orlando's Arron Afflalo and Toronto's Kyle Lowry didn't make the cut in the East.