Fred McFeely Rogers was born in Latrobe, Pennsylvania, a town located 40 miles (65 km) southeast of Pittsburgh. He was born to James and Nancy Rogers and had one sister, Elaine Crozier. Early in his life he spent much of his free time with his maternal grandfather, Fred McFeely, who would later move to Florida, and had an interest in music. He would often sing along as his mother would play the piano, and at the age of five, he began to play the piano as well.

Rogers graduated from Latrobe High School (1946). He studied at Dartmouth College in Hanover, New Hampshire, from 1946 to 1948 as a member of the class of 1950. He transferred to Rollins College in Winter Park, Florida, where he received a BA in music composition in 1951.

At Rollins, Rogers met Sara Joanne Byrd, an Oakland, Florida native. They married on June 9, 1952. They had two children, James (born in 1959) and John (born in 1961), and three grandsons, the third (Ian McFeely Rogers) born 12 days after Rogers' death. In 1963, Rogers graduated from Pittsburgh Theological Seminary and was ordained a minister in the Presbyterian Church. Scholastically, he went on to garner 40 more honorary degrees throughout his life. Rogers was red-green color blind, swam every morning, was a vegetarian, and neither smoked nor drank.

Rogers also owned a summer home on Nantucket in the village of Madaket on the western end of the island, and an apartment in New York City.

Fred Rogers had a life-changing moment when he first saw television in his parents' home. He entered seminary after college, but was diverted into television after his first experience as a viewer; he wanted to explore the potential of the medium. In an interview with CNN conducted a few years before his death, Rogers stated, "I went into television because I hated it so, and I thought there was some way of using this fabulous instrument to be of nurture to those who would watch and listen."

He thus applied for a job at NBC in New York and was accepted because of his music degree. Rogers moved to New York in 1951 and spent three years working in the production staff for music-centered programming such as NBC Opera Theater. He also worked on Gabby Hayes' show for children. Ultimately, Rogers decided that commercial television's reliance on advertisement and merchandising undermined its ability to educate or enrich young audiences, so he quit working at NBC.

In 1954, he began working at WQED, a Pittsburgh public television station, as a puppeteer on a local children's series, The Children's Corner. For the next seven years, he worked with host Josie Carey in unscripted live TV, developing many of the puppets, characters and music used in his later work, such as King Friday XIII, and Curious X the Owl.

Rogers began wearing his famous sneakers when he found them to be quieter than his work shoes when he moved about behind the set. He was also the voices behind King Friday XIII and Queen Sara Saturday (named after his wife), rulers of the neighborhood, as well as X the Owl, Henrietta Pussycat, Daniel Striped Tiger, Lady Elaine Fairchild, and Larry Horse. The show won a Sylvania Award for best children's show, and was briefly broadcast nationally on NBC.

For eight years during this period, he would leave the WQED studios during his lunch breaks to study theology at the nearby Pittsburgh Theological Seminary. Rogers, however, was not interested in preaching, and after his ordination, he was specifically charged to continue his work with children's television. He had also done work at the University of Pittsburgh's Graduate School of Child Development.

In 1963, Rogers moved to Toronto, where he was contracted by the Canadian Broadcasting Corporation (CBC) to develop a 15-minute children's television program: Misterogers [sic], which would be his debut in front of the camera. The show was a hit with children, but lasted for only three seasons on the network. Many of his famous set pieces, such as Trolley, Eiffel Tower, the 'tree', and 'castle' were all created by designers at the CBC. While on production in Canada, Rogers brought with him his friend and understudy, Ernie Coombs, who would go on to create Mr. Dressup, a very successful and long running children's show in Canada which, in many ways, was similar to Mister Rogers' Neighborhood. Mr. Dressup had also used some of the songs that would be featured on Rogers' later program.