CNN
In 1983, she was hired by CNN on the foreign desk in Atlanta, Georgia, as an entry-level desk assistant. During her early years as a correspondent, Amanpour was given her first major assignment covering the Iran-Iraq War, which led to her being transferred in 1986 to Eastern Europe to report on the fall of European communism. In 1989, she was assigned to work in Frankfurt, Germany, where she reported on the democratic revolutions sweeping Eastern Europe at the time. Through this position, she was able to move up in the company and by 1990 served as a correspondent for CNN's New York bureau.

Following Iraq's occupation of Kuwait in 1990, Amanpour's reports of the Persian Gulf War brought her wide notice while also taking the network to a new level of news coverage. Thereafter, she reported from the Bosnian war and other conflict zones. Because of her emotional delivery from Sarajevo during the Siege of Sarajevo, viewers and critics questioned her professional objectivity, claiming that many of her reports were unjustified and favoured the Bosnian Muslims, to which she replied, "There are some situations one simply cannot be neutral about, because when you are neutral you are an accomplice. Objectivity doesn't mean treating all sides equally. It means giving each side a hearing." Amanpour gained a reputation for being fearless during the Gulf and Bosnian wars from parachuting into conflict areas.

From 1992 to 2010, Amanpour was CNN's chief international correspondent as well as the anchor of Amanpour, a daily CNN interview program that aired from 2009–2010. Amanpour has reported on major crises from many of the world's hotspots, including Iraq, Afghanistan, the Palestinian territories, Iran, Israel, Pakistan, Somalia, Rwanda, and the Balkans and from the United States during Hurricane Katrina. She has secured exclusive interviews with world leaders from the Middle East to Europe to Africa and beyond, including Iranian Presidents Mohammad Khatami and Mahmoud Ahmadinejad, as well as the presidents of Afghanistan, Sudan, and Syria, among others. After 9/11, she was the first international correspondent to interview British Prime Minister Tony Blair, French President Jacques Chirac, and Pakistani President Pervez Musharraf.

From 1996 to 2005, she was contracted by 60 Minutes creator Don Hewitt to file four to five in-depth international news reports a year as a special contributor. These reports garnered her a Peabody Award in 1998 (she had earlier been awarded one in 1993). Hewitt's successor Jeff Fager was not a fan of her work and terminated her contract.

She has had many memorable moments in her television career, one of them in a live telephone interview with Yasser Arafat during the siege on his compound in March 2002, in which Arafat gave tough responses: “Are you asking me why am I under complete siege? You're a wonderful journalist. You have to respect your profession.” and “You have to be accurately when you are speaking with General Yasser Arafat. Be quiet!”, and finished by hanging up on her.

ABC News
On 18 March 2010, Amanpour announced she would leave CNN for ABC News, where she would anchor This Week. She said, “I’m thrilled to be joining the incredible team at ABC News. Being asked to anchor This Week in the superb tradition started by David Brinkley is a tremendous and rare honor, and I look forward to discussing the great domestic and international issues of the day. I leave CNN with the utmost respect, love, and admiration for the company and everyone who works here. This has been my family and shared endeavor for the past 27 years, and I am forever grateful and proud of all that we have accomplished.” She hosted her first broadcast on 1 August 2010.

During her first two months as host, the ratings for This Week reached their lowest point since 2003. On 28 February 2011, she interviewed Muammar Gaddafi and his sons Saif al-Islam and Al-Saadi Gaddafi.

On 13 December 2011, ABC announced Amanpour would be leaving her post as anchor of ABC News' This Week on 8 January 2012, and returning to CNN International, where she had previously worked for 27 years, and maintaining a reporting role at ABC News.

Return to CNN
A day later on 14 December 2011, in statements by ABC and CNN, it was announced that, in a "unique arrangement," Amanpour would begin hosting a program on CNN International in 2012, while continuing at ABC News as a global affairs anchor.

It was later revealed that in the spring of 2012, CNN International would refresh its lineup, putting the interview show Amanpour back on air. On-air promotions said she would return to CNN International on April 16. Her 30-minute New York-recorded show - to be screened twice an evening - would mean that the US parent network's Piers Morgan Tonight interview show would be 'bumped' out of its 9:00pm (Central European Time) slot to midnight (CET).