Kelly was born in Los Angeles, California. She is the only child of former Aerosmith guitarist Rick Dufay and Maureen Kelly, an exotic dancer and single mother who often moved with her daughter to different communities before settling in Albuquerque, New Mexico, by the time Minka was in junior high school. Kelly has recalled her childhood as "pretty rough". She resented Dufay, as he had abandoned her and her mother. However, at seventeen, she attempted to reconcile with him by inviting him to New Mexico. She is of Irish and French descent.
At 19, after graduating from high school, Kelly returned to Los Angeles. While on a test shoot for a modeling agency, she was approached by a former Playboy Playmate interested in managing her, and who placed Kelly as a receptionist at a surgeon's office who would provide Kelly breast augmentation in exchange for hours worked. She then attended school for a year to become a surgeon's assistant, afterwards working as a scrub tech. She spent four years in that vocation while also auditioning as an actress before landing the new NBC television drama Friday Night Lights, based on the high school football movie of that name. In the interim, she had small roles in movies and shows, including the film State's Evidence, and a recurring-guest role on the TV sitcom What I Like About You.
In preparation for her role as cheerleader Lyla Garrity on Friday Night Lights, she trained with the Pflugerville High School cheerleading squad. Kelly received praise for her acting on the series, with the The New York Times calling her performance "heartbreaking".
She shot a cameo for The Kingdom, alongside Jamie Foxx. Peter Berg, the creator and pilot director of Friday Night Lights, directed the film. Kelly was the lead actor on the The CW's 2009 pilot Body Politic which did not go to series.
Minka joined forces with Alyson Hannigan, Jaime King, Emily Deschanel, and Katharine McPhee in a video slumber party featured on FunnyorDie.com to promote regular breast cancer screenings for the organization Stand Up 2 Cancer.
Minka Kelly landed a role in the CBS comedy pilot True Love as Kate, a Midwestern girl who falls in love with Henry — part of the quartet in the ensemble show — at the top of the Empire State Building, but was replaced by Sarah Chalke.
The actress currently guest stars in the NBC primetime series Parenthood.
Minka was named 'Sexiest Woman Alive' by Esquire magazine for 2010.