Zakrzewska was born in Berlin, the eldest of six children to Ludwig Martin Zakrzewski and Caroline Fredericke Wilhelmina Urban. Her father was from a noble Polish family which had lost its wealth and property to the Russians, so he worked as a civil servant. Her grandmother was a veterinary surgeon, and her mother worked as a midwife.
After studying medicine and serving as an assistant and then as a teacher in the college in which she had studied, she left in 1853 for the United States, where she was graduated at Cleveland medical college. With Elizabeth and Emily Blackwell, she established the New York infirmary, which she superintended two years, as resident physician and manager. In 1862, Zakrzewska founded the New England Hospital for Women and Children, the first hospital in Boston, the first with a school for nurses and the second hospital in America to be run by women physicians and surgeons.
She also broke barriers that hindered women in practicing medicine in the United States, founded hospitals for women, and pioneered the movement that opened the nursing profession to black women with the first black nurse in America graduating from the school in 1879. As a feminist and abolitionist, she became friends with William Lloyd Garrison, Wendell Phillips and Karl Heinzen.