Police said in a statement the teenagers, aged 16 and 19, had been reported missing on Friday and had reportedly been spotted near the Syrian border.
"The family that reported the missing girls is deeply concerned by the purpose of the journey and fears they might have gone to Syria," the statement read "The police have launched an international search of the girls through Interpol."
The girls sent an email to their family, who have lived in Norway since 2000, to explain the reasons behind their departure.
"Muslims are currently under attack from all fronts and something needs to be done. We want to help the Muslims, and the only way to do so is to be with
them in their pains and their joy," they wrote, according to Norwegian tabloid Verdens Gang.
"It is not enough to stay at home and send money. With this in mind, we have decided to go to Syria to help by any means," they said.
The identity of the girls has not been revealed.
According to the tabloid, their family is not particularly religious, but the older girl recently became radicalised and started wearing a full-face veil, or niqab.
According to estimates from Norwegian intelligence, between 30 and 40 people have left Norway to take part in the Syrian conflict.
"Norwegian media have already reported on female cases, but a 16-year-old, that is a special case," Norwegian Police Security Service spokesman Trond Hugubakken said.