Maryland Transportation Authority Police arrested him on Interstate 95, just south of Baltimore, said Cpl. Pamela Thorne, a spokeswoman for the agency.
Authorities said Ponson was stopped for tailgating, given a field sobriety test and charged with driving under the influence and driving while impaired. At the station, he refused a breath test, which carries an automatic 120-day suspension of his license for a first offense.
The Orioles and Ponson's agent, Barry Praver, did not immediately return calls.
Ponson was charged in January with driving under the influence in Florida, and the case has not yet been resolved. That arrest came weeks after he spent 11 days in an Aruban jail for a Christmas Day fight at a beach. He apologized for the fight and reached a settlement that involved community service and a charitable contribution.
A year ago, Ponson was considered the team's ace and was the Opening Day pitcher in 2004. He is 7-11 with a 6.21 ERA and hasn't won since June 18. He has been on the disabled list with a calf strain and hasn't pitched since Aug. 7. An MRI on Wednesday found a torn thumb ligament, and he was expected to be sidelined at least three more weeks.