Rajeswari secured 477,529 votes while her nearest rival, Rudra Madhav Ray of the Bharatiya Janata Party, received 178,661 votes, state's joint chief electoral officer Jyoti Prakash Das told IANS.
Congress candidate Abhimanyu Behera stood third, securing just 90,536 votes, Das said.
The by-poll were held Oct 15. It was necessitated following the death of the BJD's Hemendra Chandra Singh. Rajeswari is his widow.
The Kandhamal Lok Sabha constituency covers seven assembly segments spread over four districts of Kandhamal, Boudh, Nayagarh and Ganjam.
BJD leaders and workers celebrated Rajeswari's victory by bursting crackers and distributing sweets in Phulbani town, district headquarters town of Kandhamal.
After the win, Rajeswari said she would work for the overall development of the region and fulfil the dream of her late husband.
"It is the victory of Chief Minister Naveen Patnaik," she told reporters.