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.
She spent four years as a reporter and anchor for WBBM-TV. Phyllis McGrady, a senior vice president at ABC, said of her: "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."
As Peter Jennings was receiving chemotherapy for his lung cancer in April 2005, she and Charles Gibson temporarily filled in for him on World News Tonight until his death in August. After a period of mourning and indecision, she and Bob Woodruff were chosen as co-anchors on December 5, 2005.
Despite Katie Couric being the first woman named to anchor an evening newscast solo, Vargas can be considered the first de facto solo woman evening news anchor given that, after Bob Woodruff's injury, she anchored almost every broadcast alone (although there was a brief period after Woodruff's injury where Vargas co-anchored WNT with either Charles Gibson or Diane Sawyer) during her short tenure as "co-anchor" of WNT.
On May 23 2006, Vargas announced her resignation from WNT. Gibson was then named sole anchor of the show, effective from May 29, 2006, replacing Vargas and her injured co-anchor Bob Woodruff. To explain the sudden change, Vargas cited her doctors' recommendation to cut back her schedule considerably due to a difficult pregnancy and her wish to spend more time with her new baby when he arrives. Most "inside accounts", however, claimed she fully expected and wished to return to the anchor chair soon after giving birth, but Gibson threatened to quit the network if he wasn't made sole permanent anchor. According to these sources, his gambit succeeded and she was left embittered, although not enough to sever ties with the network. In late 2006, Vargas returned as co-anchor of 20/20 and primary presenter of ABC News specials.