Nace Isabel Ana en Nueva York el 28 de agosto de 1774. Crece en el seno de la iglesia episcopaliana.
Contrae matrimonio con William Seton a la edad de veinte años y llega a tener cinco hijos. El 27 de diciembre de 1803 enviuda.
Años más tarde, el 14 de marzo de 1805 abraza el catolicismo, lo cual supone para ella múltiples pruebas, tanto interiores como exteriores, venidas de los parientes y amigos. Todas las supera con fe, amor y valentía.
Se aplica asiduamente a la vida espiritual. Educa con solicitud a sus hijos y, deseosa de entregarse a la actividad caritativa y educadora.
En 1809 en la diócesis de Baltimore funda el Instituto de Hermanas de la Caridad de San José, renovando la gesta de San Vicente de Paúl y Santa Luisa de Marillac. Dicho Instituto tiene por finalidad la formación de muchachas. Es la primera Congregación religiosa femenina en norteamérica.
Después de su muerte las Hermanas se unen a la Compañía de las Hijas de la Caridad de París, tal como fue su deseo desde los comienzos.
También funda la primera escuela parroquial católica en Estados Unidos.
Muere piadosamente en Emmitsburg, Maryland, el 4 de enero de 1821. Su beatificación tiene lugar el 17 de marzo de 1963, bajo el pontificado de Juan XXIII. El 14 de septiembre de 1975 es canonizada por el papa Pablo VI.
Dos grandes temas marcaron su vida espiritual: la fidelidad a la Iglesia y la eternidad de la gloria.
Es la primera santa de Estados Unidos de América. Su fiesta se celebra en el calendario de la iglesia el 4 de enero.
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