Caldwell was born in Maryville, Missouri, and grew up in Fayetteville, Arkansas. She was a child prodigy and gave public performances on the violin by the time she was ten years old. She graduated from Fayetteville High School at the age of 14.
Caldwell graduated from Hendrix College in 1944 and attended the University of Arkansas as well as the New England Conservatory of Music. She won a scholarship as a viola player at the Berkshire Music Center in 1946. In 1947, she staged Vaughan Williams's Riders to the Sea. For 11 years she served as the chief assistant to Boris Goldovsky.
Caldwell moved to Boston, Massachusetts, in 1952 and became head of the Boston University opera workshop. In 1957 she started the Boston Opera Group with $5,000. This became the Opera Company of Boston, where she staged a wide range of operas and established a reputation for producing difficult works under pressure. She was also known for putting together interesting variations on standard operas.
Highlights in Boston that she conducted and/or stage directed included Le voyage de la lune, Otello (with Tito Gobbi as Iago), Command Performance (world premiere), Manon and Faust (both with Beverly Sills and Norman Treigle), Lulu (U.S. East Coast premiere), I puritani (with Dame Joan Sutherland), Intolleranza (U.S. premiere), Boris Godunov (original version), Hippolyte et Aricie (U.S. stage premiere, with Plácido Domingo), La bohème (with Renata Tebaldi and Domingo), Moses und Aron (U.S. premiere), The Rake's Progress, Bluebeard's Castle, Carmen (with Marilyn Horne), Macbeth (original version), The Good Soldier Schweik, The Fisherman and His Wife (world premiere, with Muriel Costa-Greenspon), La finta giardiniera, Norma (with Sills), Les Troyens, Don Carlos (U.S. premiere of original French version), Don Quichotte, War and Peace (U.S. stage premiere, with Arlene Saunders), Benvenuto Cellini (U.S. premiere, with Jon Vickers), I Capuleti e i Montecchi, Montezuma (U.S. premiere), Ruslan and Ludmila (U.S. premiere), Rigoletto (with Sills, Richard Fredricks, and Susanne Marsee), Stiffelio (U.S. stage premiere), La damnation de Faust, Tosca (with Magda Olivero), La vide breve, El retablo de maese Pedro, The Ice Break (U.S. premiere), Aïda (with Shirley Verrett in the title role), Die Soldaten (U.S. premiere), The Invisible City of Kitezh, Taverner (U.S. premiere), The Makropoulos Case (with Anja Silja, William Cochran, and Chester Ludgin), Médée (in French and Greek), Dead Souls (U.S. premiere), Der Rosenkavalier (with Dame Gwyneth Jones) and, finally, The Balcony (world premiere, 1990).
In the 1980s, Opera New England, a branch of Ms. Caldwell's Opera Company of Boston, was the touring ambassador of opera to the New England states. She employed young professional singers in productions that were fully staged and with orchestra. She organized financing through local, state and federal funding which included the National Endowment for the Arts, Massachusetts Council of the Arts & Humanities, Connecticut Commission on the Arts, New Hampshire Commission of the Arts and the Maine Commission on the Arts & Humanities.
In 1976, she both conducted and directed Il barbiere di Siviglia (with Sills and Alan Titus), which was televised over PBS. She also directed John La Montaine's U.S. Bicentennial opera Be Glad Then, America with Odetta (Muse for America), Donald Gramm (various patriots), Richard Lewis (King George III), David Lloyd (Town Crier), and the Penn State University Choirs and the Pittsburgh Symphony.
In 1978, she led L'elisir d'amore at the Metropolitan, with José Carreras and Judith Blegen. She appeared with the New York Philharmonic, the Pittsburgh Symphony Orchestra, the St. Paul Chamber Orchestra, and the Boston Symphony Orchestra.
In 1979 she conducted and directed a televised production of Falstaff (with Donald Gramm).
Caldwell also directed one non-musical production, the 1981 Lincoln Center staging of Shakespeare's Macbeth, presented on cable TV in 1982. It starred Philip Anglim and Maureen Anderman, with a then-unknown Kelsey Grammer in the supporting role of Ross.
Caldwell retired in 2004.