Both of them, hailing from Pavoor in Kasargod district, have been taken into custody, police said.
They said the girl had also been taken to various places in Karnataka and raped.
The incident came to light when the girl was questioned by police recently after she was found in a hotel here along with four others late at night.
More persons are suspected to be involved and a detailed investigation has already begun, police said.
Kerala has been witness to such incidents over the last few weeks, the first being of a 17-year-old girl allegedly raped by her father and seven others at Paravoor in Ernakulam district over the last one year.
In another incident from that district, a six-year-old girl was allegedly sexually abused by her 40-year-old father for six months after she was forced to drink alcohol.
The man is absconding.
At Dharmadom in Thalassery in Kannur district, a 13-year-old girl was allegedly raped by her father, 15-year-old brother and uncles for nearly two years. One of the accused died recently.