Villanueva is a first-generation American, son of Dominican immigrants, Roberto Villanueva and Doris Mejia. He grew up in Queens before moving to New Jersey and resides in Brooklyn, which he calls home. A 6'10" (6'11" with shoes) power forward, he was drafted 7th overall by the Toronto Raptors in the 2005 NBA Draft.
He attended high school at Blair Academy, with Chicago Bulls' Luol Deng, where he earned All-American honors as a senior as well as New Jersey Co-player of the Year. He entered the NBA Draft but decided to withdraw his eligibility to attend college at the University of Connecticut.
In his first year at UConn, Villanueva was named to the Big East All-Rookie Team. In the Summer of 2004, Villanueva was a member of the gold medal-winning United States 21 and under team at the World Championships. He was also a member of the 2004 NCAA Men's Basketball National Champion Connecticut Huskies.
Villanueva had surprised many fans and sports reporters by averaging 16.9 points per game in the 2005-2006 pre-season. This led all rookies in the pre-season and surpassed the second-best rookie by 4.5 points.
Villanueva suffers from an autoimmune skin disease called alopecia areata which affects 4.7 million Americans. This results in hair loss on his scalp and elsewhere on his body, but the disease is not otherwise life-threatening or harmful. Villanueva has become a spokesman for the NAAF (National Alopecia Areata Foundation) to help others growing up with the same condition. In March 2006, the NBA recognized his efforts by giving him the league's Community Assist Award for the month of February. 
Villanueva is also known by the nicknames CV3, Charlie V. and The Big Smooth. He was a close second in the running for the 2005-2006 Rookie of the Year award.
On March 26, 2006, Villanueva set a career high and Raptors rookie record for points in a game with 48 in a 116-125 loss to the Milwaukee Bucks. His point total is the most by a rookie since Allen Iverson scored 50 in 1997.
Charlie Villanueva was selected to the 2005-06 T-Mobile NBA All-Rookie First Team, and finished 2nd in points (56) trailing only Chris Paul (58) and in front of Andrew Bogut (55), Deron Williams (46) and Channing Frye (45).
- 2005 - Named NBA Eastern Conference Rookie of the Month for December
- 2006 - Selected to compete in the 2006 T-Mobile Rookie Challenge in Houston
- His favorite NBA player is Tracy McGrady.
- His favorite actor is Denzel Washington.
- His idol growing up was Reggie Miller. His regular number is #3, but he wore #31 during the 2005-2006 as a tribute to Reggie Miller who retired in the 2004-2005 season.