Mark Podwal may have been best known initially for his drawings on The New York Times Op-Ed page. In addition, he is the author and illustrator of numerous books. Most of these works - Podwal's own as well as those he has illustrated for others - typically focus on Jewish legend, history and tradition. His art is represented in the collections of the Metropolitan Museum of Art, the Victoria and Albert Museum, the Israel Museum, Prague's National Gallery, the Jewish Museums in Berlin, Vienna, Prague, and New York, among many other venues.

Though he always loved to draw, Podwal never pursued formal art training and instead became a physician. While attending New York University School of Medicine, his passion for drawing once again crept in: the tumultuous events of the 1960's compelled Podwal to create a series of political drawings that were published as his first book The Decline and Fall of the American Empire. These images were brought to the attention of an art director at The New York Times, and in 1972, his first drawing appeared on its OP-ED page. That drawing of the Munich massacre was later exhibited at the Musée des Arts Décoratifs Palais du Louvre.

Podwal is the author and illustrator of Jerusalem Sky: Stars, Crosses and Crescents; A Sweet Year; Doctored Drawings, among others. King Solomon and His Magic Ring, in collaboration with Elie Wiesel, won a Silver Medal from the Society of Illustrators in 1999 and You Never Know, in collaboration with Francine Prose, won a National Jewish Book Award in 1998.

Fallen Angels, in collaboration with Harold Bloom, was published in 2007. Author Cynthia Ozick has given Podwal the Hebrew name Baal Kav Emet, or "Master of the True Line." As she explains in her essay Ink & Inkling, "[Podwal] joins metaphysics to physics: essence to presence; ideas to real objects...The Master of the True Line is also master of hidden meanings, of symbol and metaphor." In 1996, the French government named Podwal an Officer of the Order of Arts and Letters. Hebrew College, Newton Centre, Massachusetts, in 2003 awarded him a Doctor of Humane Letters honoris causa.

Beyond his works on paper, Podwal's artistry has been employed in an array of diverse projects, including the design of a series of decorative plates for the Metropolitan Museum of Art. His work has been engraved on a Congressional Gold Medal and woven into an Aubusson tapestry that adorned the ark in the main sanctuary of Temple Emanu-El in New York. Moreover, he designed sixteen kiln cast glass panels for the United Jewish Appeal Federation Headquarters. Podwal is represented by Forum Gallery, New York and has exhibited there since 1977. His papers are archived at Princeton University.

Mark Podwal collaborated with Academy Award winning filmmaker Allan Miller on the documentary House of Life: The Old Jewish Cemetery in Prague, narrated by Claire Bloom, which was broadcast on PBS in 2009 and 2010.

In 2011, Podwal received commissions to illustrate a new Passover Haggadah for the Central Conference of American Rabbis Press; to design new embroidered textiles for Prague's seven hundred year old Altneuschul; to create a limited edition print for The Metropolitan Opera's production of Nabucco; and to design Hanukkah cards for The Metropolitan Museum and The Metropolitan Opera. Also in 2011, he received the Jewish Cultural Achievement Award from the Foundation for Jewish Culture.

In 2014, at the Terezin Ghetto Museum there was an exhibition of Podwal’s cycle, All this has come upon us… The forty-two paintings and drawings, disturbing reminders of how Europe’s extensive history of "Jew-hatred" laid the groundwork for the Holocaust, have been published as archival pigment print portfolios. Portfolios have been acquired by the Vatican, United States Holocaust Memorial Museum, Library of Congress, Yad Vashem, the Bodleian Library, the British Library, Institute for Advanced Study, Harvard University, Yale University, Princeton University, Columbia University, Hebrew University, National Library of Israel, among many others. Czech Television produced and broadcast a documentary on Podwal's Terezin exhibition.

In 2019, the Foreign Ministry of the Czech Republic awarded Mark Podwal the prestigious Gratias Agit Prize. Podwal’s current projects include a poster for each new Metropolitan Opera season, a series on Mozart and Prague, a series Kaddish for Dąbrowa Białostocka about the Polish shtetl where his mother was born, and illustrations for Heinrich Heine's poems, Hebrew Melodies. Moreover, Glitterati Inc. published the 374 page monograph, Reimagined: 45 Years of Jewish Art by Mark Podwal.