Born in New Jersey of Italian ancestry, Micucci was raised in Nazareth, Pennsylvania, in the Lehigh Valley region of the state, where she first learned to play classical piano, taught by her mother. She graduated alongside rock musician Jordan White in 1998 from Nazareth Area High School. She then received an A.A. in Fine Arts from Keystone College in La Plume, Pennsylvania, and a B.A. in Studio Art in 2003 from Loyola Marymount University, Los Angeles. As of 2008, she resides in Los Angeles.
Her TV credits include numerous television commercials, as well as Toni the barista on NBC's 'Four Kings, guest roles on Malcolm in the Middle, Til Death, How I Met Your Mother, Cory in the House, and Campus Ladies, and recurring roles on Scrubs and Raising Hope. Her film credits include The Last Hurrah, Bart Got a Room and When in Rome. She plays "Lily the IT girl" on Elevator produced by HBO's Runawaybox. In early 2009, she released a five-track EP entitled Songs.
Micucci appeared in five episodes of Scrubs ("My Lawyer's In Love", "My Absence", "My Chief Concern", "Our Histories", and "My Finale") as Stephanie Gooch, a ukulele player with whom Ted Buckland begins a relationship. She performs her song "Mr. Moon" as well as an adapted version of "Fuck You" (retitled "Screw You" for ABC), a song she typically performs as part of the musical duo Garfunkel and Oates. In 2009, she starred in the short film Imaginary Larry, co-written and co-directed by Riki Lindhome, her partner in Garfunkel and Oates. In August 2009, Micucci appeared in an advertising campaign for Hillshire Farms, and for H & R Block in January 2010.
Performing as Garfunkel And Oates with Riki Lindhome at Upright Citizens Brigade Theater in 2009 Micucci performs "Playin' with Micucci" on third Mondays at the Steve Allen Theater on Hollywood Boulevard, in Hollywood, California, most recently in August and October 2011. In the act, she presents "songs and stories in [a] musical variety show." She says the title is the only dirty aspect of the show. She can also frequently be seen performing with Lindhome in "An Evening with Garfunkel and Oates" at the Upright Citizens Brigade Theater in Los Angeles. She performed with William H. Macy on the ukulele to promote the DVD release of the film Bart Got a Room. The video has been circulated around the Internet on sites such as YouTube and The Huffington Post. In 2010, she appeared in the Kristen Bell film When in Rome and also in an episode in the 6th season of the TV show Weeds as a slightly sedated waitress. She appeared in some episodes of the HBO series, Bored to Death, and appeared as the babysitter/dogsitter/eldersitter Shelley in the series Raising Hope. In February 2011, Kate appeared briefly in a Progressive Insurance ad as a waitress. She has also voiced a character on Pendleton Ward's animated series Adventure Time, as well as the character of Julie Kane on the Disney XD animated series Motorcity. In July 2012, Kate appeared in Written by a Kid's production Scary Smash, a Geek and Sundry creation that was executive produced by Kim Evey, Felicia Day, and Sheri Byrant.
In January 2013, Micucci's casting was announced for a recurring role on The Big Bang Theory as "a potential love interest for ... Raj." Her character, the painfully shy Lucy, debuted on February 14, 2013. Micucci appeared as a guest judge on King of the Nerds.