Krusiec was born in 1974 in the Republic of China (Taiwan). She was adopted at age 5 by a Taiwanese aunt, her father's elder sister, who had married an American. Krusiec's adoptive father renamed her Michelle Jacqueline, because he wanted her to have a French name. Krusiec studied theater at Virginia Polytechnic Institute and State University, graduating with a B.A. in 1996, and later, from the University of Oxford.

Krusiec was recruited to be one of six globe-trotting travel reporters for the Discovery Channel series Travelers in 1996. Along with Barbara Alvarez, Robin Kipp, Pearce Bunting, Patrick Michael, Foster Soloman, and later Lisa Clark, she traveled to over 50 different locations on the show. Krusiec played the 18-year-old Molly O'Brien in the Star Trek: Deep Space Nine episode "Time's Orphan". She co-starred in the NBC Saturday morning sitcom One World and played the role of Exquisite Woo on Popular. She played Mei-Ling Hwa Darling, one of the Darling family's daughters-in-law, in ABC's highly publicized dramedy, Dirty Sexy Money. She had a recurring role as "Nadine Park" on Season 4 of Fox's Fringe, and has also appeared on TV shows such as NBC's Community (as "Wu Mei", a love interest of Chevy Chase's character, Pierce Hawthorne), General Hospital as Attorney Grace Yang, The Secret Life of the American Teenager as Emily, Touch as Lanny Cheong, Nip/Tuck as Mei, CSI: Miami as Susan Lee, CSI: NY as Lisa Kim, NCIS, Grey's Anatomy, Weeds, Without A Trace, Cold Case as Kara, Monk as Maria, ER as Tong-Ye, and Titus as recurring character Nancy.

Krusiec was a Best Actress nominee in the Golden Horse Film Festival for her performance in a U.S. independent film Saving Face (2005), written and directed by Alice Wu, in which she plays a Chinese American lesbian and surgeon named Wilhelmina Pang (also known as "Wil") juggling the demands of her girlfriend, Vivian Shing (played by Lynn Chen) and pregnant mother (played by Joan Chen). She has appeared in The Mind of the Married Man as Sachiko, the massage parlor girl who gives "happy endings." Krusiec appeared in a number of feature films including Knife Fight as Shannon, Sunset Stories as Nova, Relative Insanity as Marsha, Far North as Anja, the daughter of Michelle Yeoh's character, What Happens in Vegas as Chong, Cameron Diaz's character's competitive co-worker, Dumb and Dumberer as Cindy, The River Murders as Sung Li opposite Ray Liotta, Christian Slater, and Ving Rhames, Daddy Day Care as the English Teacher, Take Me Home as Suzanne, Shuffle as Kevin's Mother, and independent film projects including Tanuj Chopra's Nice Girls Crew alongside Lynn Chen and Sheetal Sheth, Shawn Chou's Tomato and Eggs opposite Keiko Agena and Sab Shimono, and Erin Li's L.A. Coffin School opposite Elizabeth Sung and Megan Lee.