From January 2006 to May 2006, she was co-anchor of ABC's flagship broadcast World News Tonight, anchoring much of the broadcast alone after co-anchor Bob Woodruff's injury in Iraq.

Vargas was born to a Puerto Rican father and an Irish-American mother; her father was then a Colonel in the U.S. Army. She spent her youth moving from base to base in Germany, Belgium and Japan.

Vargas graduated with a Bachelor's Degree in journalism from the University of Missouri in Columbia, where she made her debut broadcast as a reporter/anchor for KOMU-TV.

Elizabeth Vargas spent four years as a reporter and anchor for WBBM-TV. Phyllis McGrady, a senior vice president at ABC, said of Vargas: "Elizabeth is one of the most flexible talents I've ever worked with. She could do interviews, and do hour-long specials that make you think, and then she'll do a great interview with P. Diddy. She is versatile.

Vargas is the first woman to anchor an evening newscast in the U.S. since Connie Chung. Vargas is the first woman of Puerto Rican and Irish American heritage to be named a network nightly news anchor. She is said to be particularly proud of an ABC special report in which she questioned why the Laci Peterson case merited more attention than two other similar cases, one involving a black woman and the other involving a Hispanic woman.

Another story she did based on the book The Da Vinci Code and the role of Mary Magdalene, created a religious debate. Vargas stated that for centuries Mary Magdalene has been portrayed as a prostitute by the church. In her story, she also questioned the role of women within the church.

In 1999, she won an Emmy Award for her coverage of the Elian Gonzalez story, and in 1998  was nominated for an Emmy Award for her 20/20 investigation into the wrongful conviction of Betty Tyson.

In April 2005, as Peter Jennings was receiving chemotherapy for his lung cancer, she and Charles Gibson temporarily filled in for him on World News Tonight until his death.

Despite Katie Couric being the first named to anchor a evening newscast solo, Elizabath Vargas can be considered the first de facto woman solo evening news anchor given the fact that after Bob Woodruff's injury, Vargas had anchored almost every broadcast solo (although there was a brief period after Woodruff's injury where Vargas co-anchored WNT with either Charles Gibson and Diane Sawyer) during her short tenture as "co-anchor" of WNT.

Elizabeth Vargas is married to Grammy award-winning singer-songwriter Marc Cohn, whom she met at the 1999 U.S. Open after being introduced by Andre Agassi. In 2003, the couple had their first child, son Zachary. In February 2006, the couple announced that Vargas is pregnant and expecting their second son, due in late summer. Cohn has two children, Max and Emily, from a previous marriage.