Quaranta was drafted eighth overall in the 2001 MLS SuperDraft by D.C. United. At 16 years, four months, Quaranta surpassed fellow DC player Bobby Convey to become the youngest player in the history of Major League Soccer, a record which would subsequently be taken by another DC player, Freddy Adu. Quaranta immediately excelled in MLS, registering five goals and one assist in just 16 games during the 2001 season. Unfortunately, in the subsequent three seasons, Quaranta was beset by injuries, and struggled to live up to his early promise. Although he started all eleven games that he played in during the 2002 season, Quaranta missed almost two-thirds of the season with injuries, and things did not improve in the following two seasons, where he played in just 13 games. With fitness restored, Quaranta returned to form in 2005, where he contributed 5 goals and 5 assists in 18 games played, and finished third highest at the club for goals scored that season. Quaranta was traded to Los Angeles Galaxy from D.C. United for a partial allocation and a conditional draft pick on August 9, 2006. In his first match with the Galaxy the next day, Quaranta entered as a substitute and scored the only goal of the match in a 1–0 win over Houston. On June 30, 2007 the Galaxy traded Quaranta to the New York Red Bulls, getting a conditional fourth round pick in the 2008 MLS SuperDraftin return. After featuring in just 3 games and 47 minutes for the team, he was waived by the Red Bulls on January 3, 2008. Quaranta returned to D.C. United on March 6, 2008. He claims to have turned down larger offers from other MLS sides, but felt he still had a point to prove at D.C. His first meaningful game back with D.C. United was as a substitute in the home leg of the quarterfinals of the CONCACAF Champions' Cup against Harbour View of Jamaica. He had two assists in the 5–0 victory. In his first regular season home game back with D.C. United on April 5, 2008, Quaranta picked up a goal and an assist. Following the 2011 season, Quaranta's option was not picked up by United, and he opted to retire. It was a very brief retirement as he quickly joined the new Premier League Soccer in India. He has claimed this is due to his salary being more than double his last MLS remuneration. However, a month later, the league was cancelled before the season began.
International
Quaranta has played internationally for the Under-17 and Under-20 United States national soccer teams, but while he was dominant for the U-17's, he was not able to secure a starting place on the U-20's. After coming back from injuries in 2005, Quaranta received his first cap for the senior team July 7, 2005 in a Gold Cup match against Cuba. He converted a penalty kick in the United States' shootout victory over Panama in the Gold Cup championship game. In 2009, Quaranta was named to the United States roster for that year's edition of the CONCACAF Gold Cup. On July 8, 2009 he scored his first international goal against Honduras during a 2–0 victory in CONCACAF Gold Cup group play.
Quaranta is married and has a daughter, Olivia Naomi Quaranta and a son, Valentino, born in 2009. Santino Quaranta and Sean Rush started the Pipeline Soccer Club, a non-profit premier soccer club in Baltimore, MD which his daughter continues to play in.
Problems with drugs
In a June 14, 2008 interview with the Washington Post, Quaranta admitted to once having an addiction to painkillers and cocaine, but after a spell in rehab, he has stopped taking both. He now has a tattoo on his arm with the date that he became sober as a constant reminder of his past struggles.
