Manfredini was born on 4 April 1897 in the small comune of Pievepelago in the Emilia-Romagna region of northern Italy. Her parents were Carlo and Maria Guerri. In 1920, shortly after marrying Riccardo Manfredini, she emigrated to Iowa, United States. The couple had four children in total; Mary Russo (1921–2020), Dante (1922–2016), Rudy (1924–1997), and Enes (born 1928). Three of them were still alive at the time of her death.
Manfredini worked in an ammunition factory during World War II, and cleaned houses until she was 90. She used to understate her age so that people wouldn’t think that she was too old to work. Her husband died in 1965 at the age of 79.
After her husband’s death, Manfredini lived alone for about 42 years until moving into a nursing home in 2007 at the age of 110. She survived colon cancer at the age of 101. She ‘danced’ at the age of 103 and was still able to shovel snow when she was 106. She was able to walk with the aid of a walker, until near her 115th birthday when she started requiring the use of a wheelchair.
Apart from three living children (aged 91, 90, and 84), she also had seven grandchildren, seven great-grandchildren, and 12 great-great-grandchildren at the time of her death.