Vadra, 52, filed her papers for the Wayanad seat in the southern state of Kerala for the Nov. 13 vote after a roadshow attended by thousands of supporters of her Congress party.
Wayanad was won by Vadra's brother Rahul Gandhi in the national election this year but he had to vacate it as he also won from a second seat in the family bastion in north India and Indian law allows candidates to retain only one.
Rahul, 54, is the leader of opposition in the lower house of parliament while their mother Sonia is a member of the upper house. Both accompanied Vadra to Wayanad.
"You stood with my brother when the whole world was turning its back against him," Vadra told supporters before filing her papers. "It is my honour to represent you if you give me a chance."
Votes polled in Wayanad will be counted on Nov. 23.
Vadra, who is known for her public speaking skills, formally entered politics in 2019 when she became a general secretary in Congress. She had, however, not contested elections so far and limited herself to campaigning for her family and the party.
"The people of Wayanad hold a special place in my heart, and I can't imagine a better representative for them than my sister, Priyanka Gandhi," Rahul said in a post in X on Tuesday.
Vadra had in June vowed not to "let the people of Wayanad feel the absence of Rahul Gandhi". More than 200 people were killed in the Wayanad region in July in landslides triggered by heavy rain.
Congress has credited the Gandhi siblings for the party's surprise recovery in the election when it doubled its tally to nearly 100 seats in the 545-member lower house after sinking to historic lows since Prime Minister Narendra Modi came to power in 2014.
Modi's Bharatiya Janata Party (BJP) could not secure an outright majority in a shock result and had to depend on regional parties to form a coalition government for a third straight term in power.
Modi and BJP accuse Congress of practicing dynastic politics for its dependence on the Gandhis, a charge the party rejects.
Congress has ruled India for 54 of its 77 years since independence from Britain, and Vadra's father, grandmother and great-grandfather were prime ministers for more than 37 of those 54 years.