Lupita Murillo grew up along the U.S.-Mexico border. She is a proud Tejana from South Texas and was the first Hispanic female anchor-reporter in the Rio Grande Valley. Her alma mater is Pan American University, now known as the University of Texas Rio Grande Valley. She began her career at KRGV Channel 5 right out of college.

She came to Tucson in 1978 and has made the Old Pueblo her home for the last 47 years. Forty-six of those years were spent at KVOA News 4 Tucson.

From crawling through drug tunnels to spending 24 hours behind bars in Arizona's worst jail, Lupita has never shied away from a story. She spent a day inside the jail to show viewers its deplorable conditions. Her efforts paid off when voters passed a bond issue to build a new jail. She also traveled to Mexico to cover elections and was the first North American reporter to enter Los Pinos, the equivalent of the White House, during the inauguration of Vicente Fox. Fox was elected the 62nd President of Mexico and became the first president to break the 70-year reign of the PRI ruling party as a member of the PAN party.

When she wasn't working on undercover assignments or chasing after criminals, Lupita could be found volunteering in the community. She believed community service was as much a part of her job as reporting the news. Among the organizations she has volunteered with are the Tucson Interfaith HIV/AIDS Network (TIHAN), the Boys & Girls Clubs of Tucson and Santa Cruz County, the University of Arizona Hispanic Alumni Association, the Father's Day Council, and the Girl Scouts of Southern Arizona. She also serves on the Advisory Board of the Mel and Enid Zuckerman College of Public Health.

Lupita has won numerous Edward R. Murrow Awards and Associated Press Awards and has also been nominated for a regional Emmy®. She has been honored by the University of Arizona Hispanic Alumni Association at its Portraits of Excellence Scholarship Dinner, the Hispanic Professional Action Committee for Outstanding Community Service, the University of Arizona Women Who Lead, and the YWCA Women on the Move. For five consecutive years, she was voted "Best Reporter" by Tucson Lifestyle magazine. She also received the Pima County Sheriff's Citizen Award, and the Mayor of Tucson proclaimed June 30, 2024, as "Lupita Murillo Day." In addition, she was named Media Person of the Year by the Public Relations Society of America. She was inducted into the Arizona Media Association Hall of Fame and received the first Community Beacon Award from the Asian American Pacific Islander Organization. Before Congressman Raúl Grijalva passed away, he entered Lupita Murillo's name into the Congressional Record in recognition of her years of service to the community and her 50 years as a broadcast journalist. Most recently, she was inducted into the Arizona Media Hall of Fame in 2025.

Lupita is known for her high heels and has chased many a bad guy wearing her blingy shoes. She officially hung up her heels on June 30, 2024.