In the pilot episode, which takes place on St. Patrick's Day 1994, Ross is brought into the ER not long before his shift, to be "treated" for drunkenness by his longtime friend, Dr. Mark Greene. Throughout the next few seasons, Ross is shown to be compassionate, though not always using the best judgment. His love of children is best seen during darker situations, such as when a child is in danger. When Peter Benton talks about how Surgeons deal with emotionally charged cases and ER doctors have it easy, Ross leaves him stunned into silence when describing cases that include a young girl who beat her mother to death, a kid who is going to lose his leg to cancer and another kid who is dying from a life of homelessness. His lack of judgment leads him to assault abusive parents in the ER, but his counseling in that case just consists of the shrink telling him not to do that again.

For his work on the series, Clooney received two Emmy Award nominations for Outstanding Lead Actor In A Drama Series in 1995 and 1996. He was also nominated for three Golden Globe Awards for Best Actor – Television Series Drama in 1995, 1996, and 1997 (losing to co-star Anthony Edwards).

In 2004, Ross was listed in Bravo's 100 Greatest TV Characters. Entertainment Weekly placed Ross in its list of the "30 Great TV Doctors and Nurses". The character was included in Fox News' list of "The Best TV Doctors For Surgeon General" and in Philadelphia Magazine's 10 Best Doctors on Television. Ross was also listed in Wetpaint's "10 Hottest Male Doctors on TV" and in BuzzFeed's "16 Hottest Doctors On Television". His relationship with Carol Hathaway was included in AOL TV's list of the "Best TV Couples of All Time" and in the same list by TV Guide.

Ross was written out of the series because Clooney wished to focus on his expanding film career. He also said that there wasn't any strong story in place for his character after Season 5. He appeared at the end of the penultimate episode of season 6, when Carol leaves Cook County to reunite with Ross in Seattle. He was reportedly asked to return briefly in season 8, to make an appearance in Anthony Edwards's last episode during Greene's funeral, but Clooney declined because he did not want his cameo appearance to overshadow the departure of a beloved character on the show. Clooney returned to ER for its 15th and final season in 2009 in a story arc beginning with Episode 328, titled "Old Times", with Julianna Margulies also returning as Hathaway.