The bus was carrying 43 seated passengers, but there were many others standing in the aisle, leading authorities to believe the death toll might rise, according to ANDINA, the state-run news agency.
Among the dead were many doctors and nurses, the agency reported.
Photos from the scene showed the mangled wreckage of the red bus in the middle of small rapids on the rocky Moche River, flanked on either side by steep green slopes.
The bus was heading from Huamacho to Trujillo when it went off the road and into the river, local police told ANDINA. Authorities believe the accident happened around 4:10 a.m. (5:10 a.m. ET), the agency reported.