Barnes, 23, edged home in a sprint finish on the 106km (66-mile) course in Stockton-on-Tees, wining in two hours 35 minutes 24 seconds.
Tinkoff rider Blythe, 26, also left it late to make a sprint for the line and win in four hours, 31 minutes and seven seconds on the 212km (112-mile) course.
"I really wanted that one," he said.
Team Sky's Alex Peters led for long periods of the race, but it was Blythe who held off former British champion Cavendish in the final 20 metres for his first British title.
Canyon-SRAM rider Barnes only returned to racing in April after spending eight months out with a broken ankle.
However, she won the battle with younger sibling Alice, who had to settle for second and a second successive Under-23 title.
World champion Lizzie Armitstead was unable to defend her title because of illness.
Hannah Barnes beat younger sister Alice by a wheel to win her first British road race title, as Adam Blythe held off Mark Cavendish for the men's crown.