From 1919 to 1923, Jones attended the High School of Practical Arts in Boston. During these years, she took night classes from the Boston Museum of Fine Arts through an annual scholarship. Additionally, she apprenticed in costume design with Grace Ripley. She held her first solo exhibition at the age of seventeen in Martha’s Vineyard. Jones began experimenting with African mask influences during her time at the Ripley Studio. From her research of African masks, Jones created costume designs for Denishawn.

From 1923 to 1927, Jones attended the School of the Museum of Fine Arts in Boston to study design, where she won the Susan Minot Lane Scholarship in Design yearly. She took night courses at the Boston Normal Art School while working towards her degree. After graduating from the School of the Museum of Fine Arts, she received her graduate degree in design from the Design Art School of Boston in 1928. Afterwards, she began working at the F. A. Foster Company in Boston and the Schumacher Company in New York City. During the summer of 1928, she attended Howard University, where she decided to focus on painting instead of design.

Jones’ teaching career began shortly after finishing college. The director of the Boston Museum School refused to hire her, telling her to find a job in the South where “her people” lived. In 1928 she was hired by Charlotte Hawkins Brown after some initial reservations, and subsequently founded the art department at Palmer Memorial Institute, a historically black prep school, in Sedalia, North Carolina. As a prep school teacher, she coached a basketball team, taught folk dancing, and played the piano for church services. In 1930, she was recruited by James Vernon Herring to join the art department at Howard University in Washington, D.C., Jones remained as professor of design and watercolor painting until her retirement in 1977. She worked to prepare her students for a competitive career in the arts by inviting working designers and artists into her classroom for workshops. While developing her own work as an artist, she became an outstanding mentor and strong advocate for African-American art and artists.

Jones continued taking classes throughout her lifetime. In 1934, she took classes on different cultural masks at Columbia University. In 1945, she received a BA in art education from Howard University, graduating magna cum laude.

Previously in 1934, Jones met Louis Vergniaud Pierre-Noel, a prominent Haitian artist, while both were students at Columbia University. They corresponded for almost 20 years before marrying in the south of France in 1953. Jones and her husband lived in Washington, D.C. and Haiti. Their frequent trips to Haiti inspired and impacted Jones’ art style significantly.

In 1937, Jones received a fellowship to study in Paris at the Académie Julian. She produced more than 30 watercolors during her year in France. In total, she completed approximately 40 paintings during her time at the Académie, utilizing the en plein air method of painting that she used throughout her career. Two paintings were accepted at the annual Salon de Printemps exhibition at the Société des Artists Français for her Parisian debut. Jones loved her time in Paris as she felt fully accepted in society as opposed to the United States at this time. The French were appreciative of paintings and talent. After she was granted an extension of her fellowship to travel to Italy, she returned to Howard University and taught watercolor painting classes.

In 1938, she produced Les Fétiches (1938), an African-inspired oil painting that is owned by the Smithsonian American Art Museum. Jones painted Les Fétiches in a Post-Cubist and Post-Primitive style. Five African masks swirl around the dark canvas. She was able to view and study many different African objects and masks at the Musée de l’Homme and galleries through her fellowship in Paris. In Les Fétiches, masks from Songye Kifwebe and Guru Dan are visible.

Jones’ Les Fétiches was instrumental in transitioning “Négritude” — a distinctly francophone artistic phenomenon — from the predominantly literary realm into the visual. Her work provided an important visual link to Négritude authors such as Aimé Césaire, Léon Damas, and Léopold Sédar Senghor. She also completed Parisian Beggar Woman with text supplied by Langston Hughes. In 1938, Jones’ first solo exhibition was hung in the Whyte Gallery and would later be exhibited at the Howard University Gallery of Art in 1948.

In 1941, Jones entered her painting Indian Shops Gay Head, Massachusetts into the Corcoran Gallery’s annual competition. At the time, the Corcoran Gallery prohibited African-American artists from entering their artworks themselves. Jones had Tabary enter her painting to circumvent the rule. Jones ended up winning the Robert Woods Bliss Award for this work of art, yet she could not pick up the award herself. Tabary had to mail the award to Jones. In spite of these issues, Jones worked harder notwithstanding the racial biases found throughout the country at this time. In 1994, the Corcoran Gallery of Art gave a public apology to Jones at the opening of the exhibition The World of Lois Mailou Jones, 50 years after Jones hid her identity.

Over the course of the next 10 years, Jones exhibited at the Phillips Collection, Seattle Art Museum, National Academy of Design, the Barnett-Aden Gallery, Pennsylvania’s Lincoln University, Howard University, galleries in New York, and the Corcoran Gallery of Art. In 1952, the book Loïs Mailou Jones: Peintures 1937–1951 was published, reproducing more than one hundred of her art pieces completed in France. At the Barnett-Aden Gallery, Jones exhibited with a group of prominent black artists, such as Jacob Lawrence and Alma Thomas. These artists and others were known as the “Little Paris Group.”

In 1954, Jones was a guest professor at Centre D’Art and Foyer des Artes Plastiques in Port-au-Prince, Haiti, where the government invited her to paint Haitian people and landscapes. Her work became energized by the bright colors. She and her husband returned there during summers for the next several years, in addition to frequent trips to France. Jones completed 42 paintings and exhibited them in her show Oeuvres des Loïs Mailou Jones Pierre-Noël, which was sponsored by the First Lady of Haiti. As a result of her paintings, Jones was given the Diplôme et Décoration de l’Ordre National “Honneur et Mérite au Grade de Chevalier.” In 1955, she unveiled portraits of the Haitian president and his wife commissioned by United States President Dwight D. Eisenhower.

In the 1960s, she exhibited at School of the Museum of Fine Arts, Boston, Cornell University, and galleries in France, New York and Washington, D.C. In 1962, she initiated Howard University’s first art student tour of France, including study at Académie de la Grande Chaumière and guided several more tours over the years.

In 1968, she documented work and interviews of contemporary Haitian artists for Howard University’s “The Black Visual Arts” research grant.

Jones received the same grant in 1970 as well. Between 1968 and 1970, she traveled to 11 African countries, which influenced her painting style. She documented and interviewed contemporary African artists in Ethiopia, Sudan, Kenya, Zaire (now known as the Democratic Republic of the Congo, Nigeria, Dahomey (today known as Benin), Ghana, Ivory Coast, Liberia, Sierra Leone, and Senegal. Her report Contemporary African Art was published in 1970 and in 1971 she delivered 1000 slides and other materials to the University as fulfillment of the project.

On May 22, 1970, Jones took part in a national day of protest in Washington, DC, that was created by Robert Morris in New York. They protested against racism and the Vietnam War. While many Washington DC artists did not paint to be political or create their own commentary on racial issues, Jones was greatly influenced by Africa and the Caribbean, which her art reflected. For example, Jones’ Moon Masque is thought to represent then-contemporary problems in Africa.

In 1973, Jones received the “Women artists of the Caribbean and Afro-American Artists” grant from Howard University. In the same year, she was awarded an honorary Doctor of Philosophy from Colorado State Christian College.

On July 29, 1984, Lois Jones Day is declared in Washington, DC.

In 1991, The National Museum of Women in the Arts held an exhibition that showcased some of Jones’ children’s books illustrations.

In 1994, The Corcoran Gallery of Art opened The World of Lois Mailou Jones exhibition with a public apology for their past racial discrimination.

In 1997, Jones’ paintings were featured in an exhibition entitled Explorations in the City of Light: African-American Artists in Paris 1945–1965 that appeared at several museums throughout the country including the New Orleans Museum of Art, the Milwaukee Art Museum, and the Studio Museum of Harlem. The exhibition also featured the works of Barbara Chase-Riboud, Edward Clark, Harold Cousins, Beauford Delaney, Herbert Gentry, and Larry Potter. The exhibition examined the importance of Paris as an artistic mecca for African-American artists during the 20 years that followed World War II.

Jones’ career began in the 1930s and she continued to produce art work until her death in 1998 at the age of 92. Her style shifted and evolved multiple times in response to influences in her life, especially her extensive travels. She worked with different mediums, techniques, and influences throughout her long career. Her extensive travels throughout Europe, Africa, and the Caribbean influenced and changed how she painted. She felt that her greatest contribution to the art world was “proof of the talent of black artists”. She wished to be known as an American painter with no labels. Her work echoes her pride in her African roots and American ancestry.

In 1998, Jones died with no immediate survivors at the age of 92 at her home in Washington, DC. She is buried on Martha’s Vineyard in the Oak Bluffs Cemetery. Howard University hosted the exhibition Remembering Lois.

In 2006, Lois Mailou Jones: The Early Works: Paintings and Patterns 1927–1937 opened at the School of the Museum of Fine Arts, Boston. The exhibition showed 30 designs and paintings from the beginning of her career.

Jones is featured in the 2017 publication, Identity Unknown: Rediscovering Seven American Women Artists. She was included in the 2018 Columbus Museum of Art exhibition and catalogue of I too sing America: the Harlem Renaissance at 100.