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Melissa was just 11 when she landed the role that would change her life, joining Michael Landon, Karen Grassle and Melissa Gilbert in Little House on the Prairie in 1974. Based on Laura Ingalls Wilder's books, the series followed the Ingalls family as they built a life on the American frontier, with Melissa playing Mary, the eldest daughter of Charles and Caroline Ingalls. Mary's story became increasingly dramatic as the series progressed. At the end of season four, the character lost her sight, a storyline that gave Melissa some of her most memorable material.

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Her performance earned her a Primetime Emmy nomination for Outstanding Lead Actress in a Drama Series in 1978. She was the only Little House on the Prairie cast member to receive an acting Emmy nomination for the show. Mary went on to endure a string of tragedies, including losing a baby in a fire, and Melissa ultimately decided to leave the series in 1981 after seven years in the role.

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Before Little House, Melissa had already started working as a child actress after a dance teacher encouraged her family to find her an agent. She appeared in commercials before landing guest roles on shows including The Brady Bunch, where she memorably played a girl who shared a kiss with Bobby Brady, as well as the television version of Shaft. 

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After leaving Walnut Grove behind, Melissa continued acting and appeared in projects including horror movie Happy Birthday to Me, Murder, She Wrote and The Equalizer. She had also won a Daytime Emmy for her performance in the ABC Afterschool Special Which Mother Is Mine?, proving there was plenty more to her career than Mary Ingalls. 

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Melissa later chose to step back from acting to focus on her family, explaining that motherhood became her priority. She married television writer and producer Michael Sloan in 1990, and the couple welcomed daughter Piper in 1991 and son Griffin in 1996. The family later moved to Canada and Melissa became a Canadian citizen in 2007. Sadly, Michael died in August 2025 after 35 years of marriage. 

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Melissa has nevertheless occasionally returned to the spotlight over the years. In 2010, she released her memoir, The Way I See It: A Look Back at My Life on Little House, sharing memories of growing up on one of television's most enduring shows. Interest in the series remains strong more than 50 years after it premiered, and Melissa even reconnected with her former onscreen sister Melissa Gilbert in late 2025 after years of distance.