Bryson took a leave of absence in June 2012 for medical tests due to seizures that were related to successive hit and run vehicular accidents.

On June 21, 2012 Bryson resigned because, "the work that [Commerce employees] do to help America’s entrepreneurs and businesses build our economy and create jobs is more important now than ever and I have come to the conclusion that I need to step down to prevent distractions from this critical mission.

In 1970, with other recent Yale Law graduates, Bryson helped found and served as legal counsel for the Natural Resources Defense Council.

[10][11] On May 31, 2011, President Barack Obama nominated Bryson to succeed Gary Locke as the United States Secretary of Commerce.

[12] Citing Bryson's environmental views, United States Senator James Inhofe, a Republican from Oklahoma, put a hold on his nomination in July.

[14] As Secretary of Commerce, Bryson co-chaired the White House Office of Manufacturing Policy with Gene Sperling.

[23] In July, it was reported that Bryson would not be criminally charged for the collisions, as they resulted from the cognitive effect of unexpected seizure.