As an art student, Holzer studied painting and admired the work of abstract artists such as Kazimir Malevich, Ad Reinhardt, Mark Rothko, and Barnett Newman. However, in the late 1970s, while at the Whitney Independent Study Program in New York City, she began focusing on public art, using text as her primary mode of expression.

Holzer has said, “I chose language because I wanted to offer content that people—not necessarily art people—could understand.”

Her earliest text, Truisms (1977–79), is made up of over 250 single-sentence declarations. Resembling existing aphorisms, maxims, and clichés, they bring together a wide range of conflicting theoretical, philosophical, and political positions. Each sentence distills a potentially difficult and contentious idea into a seemingly straightforward statement. Privileging no single viewpoint, the Truisms examine the social construction of beliefs, mores, and truths.

Between 1977 and 2001, Holzer wrote 13 unique text series, which she has presented to the public in a wide array of media. In the wake of the events of September 11, 2001, she began researching U.S. government documents released under the Freedom of Information Act to learn more about 9/11 and the subsequent invasion of the Middle East. Holzer has sourced material from George W. Bush–era U.S. military initiatives in Iraq and from the Guantánamo Bay detention camp, as well as FBI and other documents concerning terrorist threats and cyber counterintelligence. Among the materials are memoranda, autopsy reports, maps, diplomatic communiqués, interrogation records, and handwritten appeals from detainees. The content from these documents has been faithfully reproduced as oil paintings, programmed in LED signs, and presented in light projections.

The early 2000s also signaled a shift in Holzer’s practice from exclusively using self-authored texts to incorporating poetry and prose written by others. She has frequently used works by Fadhil Al-Azzawi, Yehuda Amichai, Joseph Brodsky, Henri Cole, Mahmoud Darwish, Anna Świrszczyńska, Wisława Szymborska, and Adam Zagajewski. More recently, Holzer has partnered with nonprofit organizations, including Human Rights Watch, Save the Children, the Office of the United Nations High Commissioner for Refugees, the Not Forgotten Association, and Protect Our Defenders, to source first-person testimonies from people all over the world whose stories shed light on the violence and injustices that afflict too many, as well as the courage and hope that persevere.