Avalos' first major work was Illness and Health Care in the Ancient Near East: The Role of the Temple in Greece, Mesopotamia, and Israel (1995), published in the Harvard Semitic Monograph series. The book was the first to combine systematically critical biblical studies with medical anthropology to reconstruct the health care systems of Greece, Mesopotamia, and Israel.In Health Care and the Rise of Christianity (1999) Avalos outlined the thesis that Christianity began, in part, as a health care reform movement that sought to address the problems voiced by patients in the Greco-Roman world.

Since 2004, Avalos had turned his attention to the study of U.S. Latinos, the name given to people who live in the United States and trace their ancestry to the Spanish-speaking countries of Latin America. Latinos are now the largest "minority" in the United States, numbering over 40 million persons. By then, Avalos also served as General Editor of Religion in the Americas book series for Brill Publishers. He was the editor of, and a contributor to, Introduction to the U.S. Latina and Latino Religious Experience (2004), which aimed to be the first general textbook on U.S. Latino/a religions. It was unusual because it covered groups such as Dominicans and Central Americans, which most other books on Latino religion usually overlook.

His book Fighting Words: The Origins of Religious Violence (2005) used scarce resource theory to explain the role of religion in violence. Avalos argues that all conflict is usually the result of some resource that is either scarce or perceived to be scarce. This could range from love in a family to energy on a global scale. When religion causes violence, it does so because it has created a new scarce resource somewhere. Such scarce resources could include sacred space ("The Holy Land"), group privileging, and eternal life. Violence may result from the effort to maintain or acquire these religiously-created resources, and people may be willing to give or take life in pursuit of these resources. However, unlike scarcities that are verifiable (e.g., water, oil), resources such as eternal life are unverifiable and created entirely by religious bellief. Therefore, when one kills for religious reasons, one is usually trading actual lives for resources that are either not scarce or cannot even be verified to exist. He made the further argument that religious violence is always immoral, whereas secular violence is only sometimes immoral. The book also offered a scathing critique of religionist scholars who defended biblical violence and genocide, as well as a critique of the thesis that the Nazi Holocaust was an example of atheistic violence. Avalos and his book were featured on National Public Radio's Talk of the Nation on August 22, 2005.

The same year, Avalos published Strangers in Our Own Land: Religion in U.S. Latina/o Literature (2005), which was the first systematic study of how Latino authors address issues of religion and specific religions (e.g., Judaism, Islam, Protestantism, Catholicism, African Religions, and Indigenous religions).

In 2007 Avalos published The End of Biblical Studies (2007) where he argued that academic biblical scholarship was primarily an apologetic religionist enterprise meant to provide the illusion that the Bible was still a culturally and morally superior authority. He critiqued numerous fields (translation, archaeology, history, textual criticism, literary aesthetics) arguing the discipline was permeated with pro-religionist biases. John Merrill of the Biblical Archaeology Review writes that "instead of being constructive, Avalos’s arguments come off in the end as an exercise in emotional nihilism whose conclusions seem ultimately self-defeating."

This Abled Body: Rethinking Disabilities in Biblical Studies, published also in 2007, saw Avalos returning to health care studies. He contributed to, and co-edited (with Sarah Melcher and Jeremy Schipper), an anthology that explores how biblical authors conceptualize the human body and deviations from "normative" views of the human body.

In addition to books, Avalos has published dozens of articles in peer reviewed and semi-scholarly periodicals (e.g., Journal of Biblical Literature, Journal of Hispanic/Latino Theology, Catholic Biblical Quarterly, and Traditio), as well as in standard reference books such as The Anchor Bible Dictionary (1992), The Oxford Companion to the Bible (1993), The Oxford Encyclopedia of Archaeology in the Near East (1996), Eerdmans Dictionary of the Bible (2000), and The New Interpreter's Dictionary of the Bible (2006—).The subjects have ranged from Astronomy and the Bible to targumic textual criticism.

Helmut Koester, who is currently Morison Research Professor of Divinity and Winn Research Professor of Ecclesiastical History at Harvard Divinity School, argues that Avalos reveals "a deep ignorance" of the realities of American religious life and Biblical scholarship in general. In Koester's review of Avalos' book, "The End of Biblical Studies", he writes:

Perhaps I should not be surprised that a scholar who has advocated a Biblical nihilism and has recommended that Biblical Studies should be ‘tasked with eliminating completely the influence of the Bible in the modern world’ would launch an attack on the discipline of Biblical archaeology and on a magazine that is Biblical archaeology’s most important outlet...What would be required for such an endeavor, however, is knowledge of the realities of American religious life and Biblical scholarship in general, as well as the details of the controversial issues in present debates. Unfortunately Professor Avalos reveals a deep ignorance in both respects.

Avalos responded to Koester's criticisms in an essay titled, "Prof. Helmut Koester: A Reality Check for Him," where he claims that Koester had not read his book, but was working with extracts.