Gayle Connelly Manchin, 76, is in a “stable condition” in hospital where she will stay over the next few days, the senator said in a statement on Tuesday.
“On Monday, my wife Gayle and her colleague Guy Land were involved in a car accident on the way from the airport to the hotel in Birmingham, Alabama for an Appalachian Regional Commission event that was planned for today,” Mr Manchin said.
“Both were admitted to UAB Hospital and are receiving excellent care. She remains in stable condition but will stay there for a couple of days for precautionary measures,” he said.
The senator went on to thanks “the first responders who answered the call and were first on-site to provide assistance and support”.
Ms Conelly Manchin is currently the federal co-chair of the Appalachian Regional Commission.
She served as first lady of West Virginia when Mr Manchin served as governor between 2005 and 2010.
Prior to this, she was the state’s secretary of education and the arts under Republican governor Jim Justice between 2017 and 2018.
From 2013 until the following year, she served as the president of the state’s board of education.
Mr Manchin announced in November that he wouldn’t be seeking re-election, almost certainly handing his seat to Republicans in the deep-red state.
He has revealed that he’s considering a run for president, with some observers saying that, if he runs as an independent, he could help hand the White House to former president Donald Trump.
In October, Mr Manchin told reporters that “the two-party system, unless it changes, will be the downfall of our country”.
This month, he indicated that all would be revealed by Super Tuesday.
“If there’s going to be an option or a need for an option, you’ll find out by then,” he told reporters in reference to the date in early March.
“By March, you’re going to have pretty much a lay of the land and what you’re going to have and what you’re going to be offered,” he added.