Clooney was raised a strict Roman Catholic but said in 2006 that he did not know if he believed "in Heaven, or even God." He has said, "Yes, we were Catholic, big-time, whole family, whole group." He began his education at the Blessed Sacrament School in Fort Mitchell, Kentucky. He attended St. Michael's School in Worthington, Ohio; then Western Row Elementary School (a public school) in Mason, Ohio, from 1968 to 1974; and St. Susanna School in Mason, where he served as an altar boy. The Clooneys moved back to Kentucky when George was midway through the seventh grade. In middle school, Clooney developed Bell's palsy, a medical condition that partially paralyzes the face. The malady went away within a year. In an interview with Larry King, he stated that "yes, it goes away. It takes about nine months to go away. It was the first year of high school, which was a bad time for having half your face paralyzed." He also described one positive outcome of the condition: "It's probably a great thing that it happened to me because it forced me to engage in a series of making fun of myself. And I think that's an important part of being famous. The practical jokes have to be aimed at you."
Clooney next appeared in The Good German (2006), a film noir directed by Soderbergh that is set in post-World War II Germany. In August 2006, Clooney and Heslov started the production company Smokehouse Pictures. In October 2006, Clooney received the American Cinematheque Award, which honors someone in the entertainment industry who has made "a significant contribution to the art of motion pictures". On January 22, 2008, Clooney was nominated for an Academy Award for Best Actor for Michael Clayton (2007) but did not win. Later that year, he directed his third film, Leatherheads, in which he also starred. On April 4, 2008, Variety reported that Clooney had quietly resigned from the Writers Guild of America over a dispute concerning Leatherheads. Clooney, who is the director, producer, and star of the film, claimed that he had contributed in writing "all but two scenes" of it, and requested a writing credit alongside Duncan Brantley and Rick Reilly, who had worked on the screenplay for 17 years. Clooney lost an arbitration vote 2–1, and withdrew from the union over the decision. He became a "financial core status" non-member, meaning he no longer has voting rights, and cannot run for office or attend membership meetings, according to the WGA's constitution.
Clooney has advocated a resolution of the Darfur conflict. He spoke at a 2006 Save Darfur rally in Washington, D.C. In April 2006, he spent ten days in Chad and Sudan with his father to make the TV special "A Journey to Darfur" reflecting the situation of Darfur's refugees, and advocated for action. The documentary was broadcast on American cable TV as well as in the UK and France. In 2008, it was released on DVD with the sale proceeds being donated to the International Rescue Committee. In September of the same year, he spoke to the UN Security Council with Nobel Prize-winner Elie Wiesel to ask the UN to find a solution to the conflict and to help the people of Darfur. In December, he visited China and Egypt with Don Cheadle and two Olympic winners to ask both governments to pressure Sudan's government.
Clooney dated actress Kelly Preston (1987–1989). During this relationship, he purchased a Vietnamese pot-bellied pig named Max as a gift for Preston, but when their relationship ended, Clooney kept the pig for an additional 18 years until Max died in 2006. He has jokingly referred to Max as the longest relationship he had ever had.