Weir was born in Milwaukee, Wisconsin in 1967. He has a degree in journalism and creative writing from Pepperdine University in Malibu, California.

Weir began his career in 1991 as a general assignment reporter and weekend sportscaster at KAAL in Austin, Minnesota. Weir next became the sports anchor at WLUK in Green Bay, Wisconsin, and went on to anchor the WGN Morning News on WGN in Chicago from 1995 to 1998. Weir was sports anchor at KABC-TV in Los Angeles from 1998 to 2002, where he hosted the popular weekly Monday Night Live program which aired after Monday Night Football. Between 2002 and 2004, he developed, wrote and hosted three television pilots for the USA and FX Networks.

Since Weir joined ABC News in 2004, he has traveled the planet to cover breaking news and uncover global trends such as reporting on the economic rise of China and India were signature features on Good Morning America. World News devoted air time to his reports from Africa, the Middle East and the South Pacific. He waded through the floodwaters of New Orleans after Hurricane Katrina, dodged Taliban bullets in Afghanistan in 2010 and led the network's coverage of Iraq, Where Things Stand at the height of the American troop surge. Weir has anchored several launches and landings of the Space Shuttle, was the first American to broadcast live from Tibet and led off 2007's Earth Day special with an unprecedented underwater live report from the Great Barrier Reef.

In June 2007, Weir was named anchor of the short-lived ABC News magazine "iCaught." As a writer and anchor, he produced special hours for the network on topics ranging from religion to brain science to the rise and fall of General Motors.

In July 2010, he was named co-anchor on Nightline, replacing Martin Bashir. His tenure as a co-anchor began on August 9, 2010.