Antonija Höffern, née Baraga, was born on February 4, 1803, in Knežja Vas in the Duchy of Carniola, now part of modern-day Slovenia, to Janez Nepomuk Baraga, a minor noble and caretaker of Mirna Castle, and his wife Marija Katarina Jožefa.

After her parents' deaths in 1812, she and her siblings, including brother Frederic and sister Amalija, were adopted by family friend Jurij Dolinar, a prominent Ljubljana lawyer, and his wife Ana, who ensured her excellent education, making her fluent in five languages.

She married financier Feliks Höffern-Saalfeld on May 31, 1824, in Ljubljana Cathedral, but he died suddenly on February 6, 1830; rumors linked her romantically to writer Matija Čop until his drowning death in 1835, though the engagement remains disputed.

In 1837, inspired by her brother Frederic's missionary work with the Ojibwe in the United States, she became the first Slovenian woman to immigrate there, traveling via Paris and New York to join him first at Mackinac Island, Michigan, and then La Pointe, Wisconsin.

She assisted as housekeeper, teacher, and lay missionary among the Ojibwe, documenting her experiences in vivid letters to her sister describing American landscapes like the Hudson River and Niagara Falls, as well as the indigenous people's appearance and customs, though she struggled with frontier life accustomed to salon society.

Health issues prompted her departure in 1839 for Philadelphia, where, with help from academics I. C. Oehlschlager and Charles Minnigerode, she founded the elite Ladies' Institute, teaching music, languages including English, German, French, Italian, and Spanish, and handicrafts to girls.

Financial difficulties closed the school in 1854, leading Antonija Höffern to relocate to Rome, where she established and long directed a similar girls' institute. She eventually returned to Ljubljana, living modestly there until her death on May 21, 1871.