Tulloch played the small role of Norma, an Actress in the 1920s starring in a silent movie with a veteran actor, in the award-winning movie The Artist with Jean Dujardin, John Goodman and James Cromwell, which was released by The Weinstein Company in November 2011, and won the 2012 Academy Award for Best Picture. The cast of the movie was nominated for a Critics' Choice Award for Best Ensemble Cast.

Tulloch's first acting credit was as R2-D2's "girlfriend" in R2-D2: Beneath the Dome, a mockumentary produced by George Lucas telling the life story of the fictional robot R2-D2 from the Star Wars film series. She starred as "Sally" in the premiere of Sam Forman's play, Quarterlife, which opened at the Pico Playhouse in March 2006. The Los Angeles Times wrote, "Superbly performed…the scene at the end of the play, between Sally (Bitsie Tulloch) and Jack (Clark Freeman), was heartbreaking and beautiful… The lead Actress, Bitsie Tulloch, [was] absolutely brilliant."

Tulloch was nominated for a 28th Annual LA Weekly Theater Award for her performance in Sam Forman's play, Quarterlife (March 2007). Quarterlife was an experimental sequence of 20+ episodes which were originally intended to be released only on the internet, but its success led it to being picked up by NBC.

Tulloch played the lead role in Ed Zwick and Marshall Herskovitz's drama quarterlife, which premiered on NBC in early 2008. While the series was quickly pulled and moved to Bravo, Tulloch was hailed for her performance. The Los Angeles Times wrote: "She's the best realized of the bunch... Tulloch, who plays her, seems destined to be better known." She was often compared to the 'next' Claire Danes: "Will this be the first online show to create a real star? It looks likely: The gorgeous 26-year-old Tulloch clearly possesses Danes-like smarts and magnetism."

In 2009, Tulloch shot one of the 3 leads in HBO's buzzed-about comedy pilot Washingtonienne based on the book by Jessica Cutler. The pilot was produced by HBO and Sarah Jessica Parker. In early 2010 she filmed Most Likely to Succeed, a 1/2 hour comedy pilot for Imagine Entertainment through the FOX network, and a recurring role on NBC's Outlaw.

In early 2012, Tulloch was nominated by the Broadcast Film Critics Association Awards, commonly called the Critics' Choice Awards, for Best Ensemble Cast for The Artist.

Tulloch played Marilyn Sitzman, a witness to the Kennedy assassination, in the star-studded 2013 film Parkland, opposite Paul Giamatti, Billy Bob Thornton, Marcia Gay Harden, Jacki Weaver, Jackie Earle Haley, and Zac Efron. The film was produced by Tom Hanks and Gary Goetzman of Playtone, and was released in 2013, to coincide with the 50th anniversary of John F. Kennedy's assassination.

In December 2014, Tulloch confirmed she was in a relationship with her Grimm co-star David Giuntoli. In July 2016, she and Giuntoli revealed they became engaged in April 2016. They married in June 2017.