She attended the Modern School and St Christopher School, Letchworth and the women-only Newnham College, Cambridge from 1921, a constituent college of the University of Cambridge, where she studied English and history, though women were not eligible to receive a degree from the university until 1921.
She took a position teaching English at King Alfred School in Hampstead in 1929. During World War II, she left her teaching position and worked assisting Jewish refugees and London air-raid victims for the Assistance Board. She later worked in government positions for the Board of Trade and the Ministry of Information.
Through Newnham's principal Pernel Strachey, sister of Lytton Strachey, she met Edith Sitwell and Virginia Woolf, who would later call her first novel Virginia Water (1929) "a sweet white grape of a book". Positive reviews for the novel led to a deal with Victor Gollancz Ltd to publish three more books.
Her 1934 novel Harriet, about a woman whose relatives attempt to starve her to death to get to her inheritance, won the Prix Femina. The novels Doubtful Joy followed in 1935 and The Phoenix' Nest in 1936. Other novels include Robert and Helen (1944) and The Tortoise and the Hare (1954). The latter book, about a marriage that was deeply troubled despite surface appearances, was praised by Hilary Mantel of The Sunday Times as showing that Jenkins "seems to know a good deal about how women think and how their lives are arranged".
Jenkins published biographies of Lady Caroline Lamb in 1932 and of Jane Austen in 1938. She was involved in the establishment of the Jane Austen Society in 1940 and worked to purchase Austen's home in Chawton where she wrote Emma and other novels, and which later became the site of Jane Austen's House Museum.
Her 1958 biography Elizabeth the Great "showed her biographical talents at their most effective" and provided what The New York Times called "a psychological dimension to her portrait that other historians had scanted", an attribute that could also be seen in her 1960 book Joseph Lister. A. L. Rowse said that her biography of Elizabeth I "got nearer to penetrating the secret of the most remarkable woman in history than any other". In her 1961 book Elizabeth and Leicester, Jenkins presented her hypothesis that the violent ends of Anne Boleyn and Catherine Howard had made Elizabeth unable to establish a full sexual relationship with Robert Dudley, 1st Earl of Leicester, because she associated sex with death.
Her 1972 book Dr. Gully's Story, Jenkins' favourite, retold the story of the 19th-century physician James Manby Gully, whose affair with Florence Bravo, and the subsequent poisoning death of her husband Charles Bravo, led to never-proven suspicions that Gully had committed murder.
In all, Jenkins wrote a dozen novels and a dozen biographies. Her 2004 memoir The View from Downshire Hill recounted her decades of living in a Regency architecture home she bought in Hampstead. She moved into the house in 1939 and decorated it with Regency style furniture that she had acquired inexpensively in the years following World War II from period houses that had been damaged during the war. She would later say that, based on her decor, "people assumed I was comfortably off, instead of being very hard up".