Vassilieva was born in Minneapolis, Minnesota, the daughter of Russian immigrant parents Larissa, a biologist, and Vladimir Vassiliev, a physicist. At the age of seven, she was discovered at the International Modeling and Talent Association (IMTA) in New York where she won the title of Child Actress and first runner-up Child Model Of The Year 2000.
In less than one year she had the part of Elena—the granddaughter of a retired Russian General—in the episode "Deadline" of the CBS television series The Agency (2001-2003). In 2002, she played Cindy Brady in The Brady Bunch in the White House (2002) opposite Shelley Long and Gary Cole; a little girl named Gina in Inhabited (2003) opposite Malcolm McDowell; and The Bad Seed's former child actress Patty McCormack.
In 2003, she played the children's book heroine Eloise, in two made-for-television movies Eloise at the Plaza and Eloise at Christmastime directed by Kevin Lima, with Julie Andrews as Nanny. At age 11, in May 2004, Sofia began playing the role of Ariel DuBois in Medium.
She was a presenter of Family Feature Film on the Humane Society's 19th Genesis Awards in 2005. Vassilieva was nominated in 2005 for a SyFy Portal Genre Award as best young actor/actress for her role in Medium (but lost the award to Harry Potter's Daniel Radcliffe). She won a Young Artist Award in 2006 for best supporting actress in a TV Drama for her role in Medium.
Sofia had a leading role in the 2009 screen adaption of the novel My Sister's Keeper, written by Jodi Picoult, alongside Cameron Diaz, Jason Patric and Abigail Breslin. The film was directed by Nick Cassavetes. Sofia shaved her head and eyebrows for her role as Kate. She also speaks English (native), Russian (native), and French fluently.