Mark Greene, M.D. is a fictional character from the American medical drama series ER. Portrayed by actor Anthony Edwards, he first appeared in the series' pilot episode, as well as subsequently appearing as one of the principal characters until the end of the eighth season. Edwards later returned to make a guest appearance in the fifteenth season episode "Heal Thyself".

Considered to be the lead protagonist of the series’ first eight seasons, Greene's role was that of a mediator and occasional authority figure. He begins the series as the ER's chief resident, before being promoted to an attending physician. He became the only member of the original set of main characters who died during the series.

Mark Greene, an only child, was raised by his mother, Ruth (portrayed by Bonnie Bartlett), and father, David (portrayed by John Cullum). David Greene served in the United States Navy, and thus the family moved frequently and lived all over the country, including Jacksonville, Florida, Norfolk, Virginia, Corpus Christi, Texas, Washington D.C., Kings Bay, Georgia, and Hawaii, where they spent three years, David's longest assignment. Greene had a difficult relationship with his father; as a youth he rebelled to upset his father and he set goals different from what he believed his father wanted. He felt his father favored his Navy career over his family, only to learn in adulthood that David turned down a promotional track to Admiralship to come home and help Greene deal with a bully. The family's time spent in Hawaii was the most memorable for Greene and he attempted to recreate this with his daughter Rachel during the last few weeks of his life.

During high school Greene developed a romantic relationship with Jennifer, who would go on to become his first wife. Their daughter, Rachel, was born shortly after they married. During medical school he met and befriended future colleague Doug Ross. Greene completed his internship and residency in the Emergency Department of County General Hospital in Chicago, Illinois, and then became Chief Resident of the Emergency Department. Greene developed close friendships with Susan Lewis and Carol Hathaway, and continued his friendship with Ross. Greene's marriage to Jennifer is strained by his workload and by her decision to complete law school, which monopolizes much of her time.

In the pilot episode, which takes place on St. Patrick's Day 1994, Greene, the chief resident, is awakened in the first scene to help Ross, the emergency pediatric fellow who often comes in on his nights off to sober up after carousing. His close friendship with Lewis is also shown as they confide in each other about their personal lives while on break. During the same episode, Jennifer convinces Greene to visit a private practice near the hospital in hopes he will change careers for more family-friendly hours. Greene decides against this career change. During his night shift at the ER, Greene urges the staff to return to work after Hathaway is rushed in due to a suicide attempt.

During the first season, Greene's marriage is increasingly strained. When offered an attending physician's position by David Morgenstern, Greene accepts. Jennifer has been clerking for a judge in Milwaukee and becomes increasingly tired of commuting and living separately to accommodate Greene's career. She begins an affair with a coworker, and the marriage soon ends, with Rachel and Jennifer leaving Chicago first for Milwaukee and later for St. Louis.

In "Love's Labor Lost", Greene miscalculates treatment of a pregnant woman that leads to her death in childbirth; the aftereffects of Greene's judgment continue into the second season.

In "A Miracle Happens Here", a Christmas episode, Greene explains that he is the son of an agnostic Jew and a lapsed Catholic. He lights a Hanukkah candle for a Holocaust survivor. Greene understands some Yiddish.