As a teenager and young adult, Rice took classes at the improvisational comedy enterprise Second City and played hockey for his high school. He has also been playing the guitar since he was a child. One of his cousins is Lauren Collins, one of the stars of Degrassi: The Next Generation. He is also first cousin to the late Seinfeld writer Marjorie Gross.
Rice was raised in a secular Jewish family and attended Crescent School, a Toronto boys' independent school, for elementary school and then went to high school at Forest Hill Collegiate Institute. Rice pursued film studies at Glendon College, York University in Toronto.
After graduating from university Rice spent his efforts working as an assistant director and independent film-maker.
In 1993, Rice directed a short film entitled Telewhore, a documentary about a phone sex girl. It was exhibited at The Toronto International Film Festival and was well-received by critics. In 1994, Rice and Kenny Hotz, who had been friends since childhood, collaborated on the short film It Don't Cost Nothin' to Say Good Morning. Their first feature-length film was Pitch in 1997, which won Best Film Award from the Toronto Independent Arts Festival. In 2000 Rice directed, produced and wrote a short film for TV entitled Something Anything which won a Telefest Independent Television Festival award for best comedy. There was interest from the television station that had broadcast the short film, to turn it into a TV series but the idea was later scrapped.
Rice also performed stand-up comedy in Canada.
In 2003, Rice and Hotz created the show Kenny vs. Spenny, which finished its sixth season in 2010 and ended with an hour-long series finale on December 23, 2010. The show aired in many different countries and was nominated for Gemini Awards in 2004, 2005, 2006, and 2008, it even caught the attention of South Park creators Trey Parker and Matt Stone who became executive producers of the show from season 4 onwards.
In 2008, Spencer Rice wrote and starred in the mockumentary film Confessions of a Porn Addict in which he played the character Mark Tobias.
Rice's next project was called Single White Spenny. He played himself, inspired by genuine events in his life, but exaggerated for comedic effect. However, Showcase announced that Single White Spenny had been cancelled after one season due to low ratings and its inability to capture Kenny vs. Spenny audiences.
In August 2012, Rice announced on his Facebook page that he has created a brand new show called X Rayted. The show will be a documentary about the porn industry focusing on the main character trying to beat the world record for how many women he can have sex with within 24 hours. Rice suggested his appearance only be small as he will be mainly the writer and director of the project. Unlike Rice's other projects, X Rayted is not a fictitious piece and is entirely real. However, Rice said that there are comic elements in the show, but they come from real people just being themselves. The show ran for 8 episodes in 2013.