In 1976, Naomi Janowitz and Wenig self-published Siddur Nashim: A book of Sabbath Prayers for Women, which referred to God using female pronouns and imagery, and was the first Sabbath prayer book to do so. Wenig earned her B.A. from Brown University in 1978, and was ordained by Hebrew Union College-Jewish Institute of Religion in 1984. She was the rabbi of Beth Am in New York City from 1984 until 2000. She began as an instructor of liturgy and homiletics at Hebrew Union College-Jewish Institute of Religion in 1985.
She is openly lesbian, and due to a resolution proposed by her and student rabbi Margaret Holub for the June 1986 Convention of the Central Conference of American Rabbis, an Ad Hoc Committee on "Homosexuality and the Rabbinate" was formed. This committee eventually issued a report in 1990 which declared (among other things) that "all rabbis, regardless of sexual orientation, [should] be accorded the opportunity to fulfill the sacred vocation that they have chosen." The committee also endorsed the view that "all Jews are religiously equal regardless of their sexual orientation."  In 1990, the Central Conference of American Rabbis endorsed this report. In 1995, Wenig's essay "Truly Welcoming Lesbian and Gay Jews" was published in The Jewish Condition: Essays on Contemporary Judaism Honoring Rabbi Alexander M. Schindler; it was the first published argument to the Jewish community on behalf of civil marriage for gay couples. This essay and Wenig's "Tribute [to Rabbi Alexander M. Schindler]" in Kulanu (All of Us): A Program for Congregations Implementing Gay and Lesbian Inclusion, A Handbook for UAHC Congregations (1996) are the first published histories of the Reform Jewish movement's acceptance of lesbian and gay rights. Also in 1995, Margaret Wenig, along with Rabbi Sharon Kleinbaum and Russell Pearce, sent a resolution asking for support for civil marriage for gay couples to the Reform movement's Commission on Social Action; when it was approved by them, Wenig submitted it to the Central Conference of American Rabbis, which approved it in 1996.
In 1990 she wrote the sermon, "God Is a Woman and She Is Growing Older," which as of 2011 has been published ten times (three times in German) and preached by rabbis from Australia to California. It was also aired on Chicago Public Television and the Odyssey channel, and won a Harper Collins Best Sermons Award in 1991.
In 1991 she became the first female rabbi to be accepted as a member of the Academy of Homiletics.
In 2002 at Hebrew Union College-Jewish Institute of Religion in New York Wenig organized the first school-wide seminar at any rabbinical school which addressed the psychological, legal, and religious issues affecting people who are intersex or transsexual. In 2003 she organized the first school-wide seminar at the Reconstructionist Rabbinical College which addressed the psychological, legal, and religious issues affecting people who are intersex or transsexual.
In June 2012 Wenig served as the first female Scholar-In-Residence for the Rabbinical Association of Greater Miami’s Annual Sermon Seminar.
In 2015 she was inaugurated as the first Jewish President of the Academy of Homiletics.
Wenig, along with Dr. Miriam Frank, PhD, is a coauthor of the booklet "When Madness Comes Home: Living in the Shadow of a Loved One's Serious Mental Illness."
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- "HUC-JIR Faculty Member Inaugurated as First Jewish President of the Academy of Homiletics".