One of her main opponents will be the leader of Thailand's military junta, Prayuth Chan-Ocha, who has been in power since a military coup in 2014.
The general election this March will pit Thailand's royalist-military establishment against the populist movement - led by ousted Prime Minister Thaksin Shinawatra.
Thailand's King Vajiralongkorn has denounced as "inappropriate" his sister's unprecedented bid to run for prime minister in March's election. She relinquished her royal title when she married her American husband Peter Ladd Jensen in 1972 and settled in the USA, where she studied biochemistry.
"Who would dare criticize a royal prime minister?" said Puangthong Pawakapan, professor of political science at Chulalongkorn University.
Despite his grim record, Prayut had been widely expected to win next month's election, if only due to the lack of a credible challenger.
His populist policies delivered him unmatchable electoral majorities, but he was resented by the traditional ruling class, including royalists and the military, and the army deposed him in a 2006 coup.
Many Thais had assumed that the princess would not have sought the nomination without her brother's blessing and were surprised that he would have supported her association with a party that is considered unsympathetic to the monarchy.
2018: Pictures appear on social media of Ubolratana, Thaksin and his sister, former prime minister Yingluck Shinawatra, at the World Cup in Russian Federation.
The party falls under the tutelage of Thaksin, a billionaire self-exiled former premier, who stands at the heart of Thailand's bitter political schism - loathed by the army and Bangkok elite, yet adored by the rural poor.More news: Check your compass: The magnetic north pole is on the move
"All royal family members adhere to the same principles ... and can not take any political office, because it contradicts the intention of the constitution", he added.
Thai Raksa Chart party leader Preechapol Pongpanich, holds up application of candidate for prime minister, Princess Ubolratana Rajakanya Sirivadhana Varnavadi, at the election commission office in Bangkok on February 8.
Analysts said she is not technically covered by the kingdom's royal defamation law - which carries heavy jail sentences -but given the culture of deference to royalty, she is unlikely to face the scrutiny given to most politicians.
Rivalry between the Bangkok-centred, royalist elites and Thaksin and his rural-based supporters has brought street protests, military coups, and violent clashes over nearly 15 years.
In 2016, Thais voted to approve a new constitution created by the country's military leaders, which was designed to perpetuate military influence and block Mr Thaksin's allies from winning another election.
But her foray into politics - breaking with royal tradition - looked to be short-lived after her younger brother, King Maha Vajiralongkorn, quickly signaled he opposed it, which is likely to lead to her disqualification.
"Just a theory: Thaksin creates Thai Raksa Chart to mitigate the risk of Puea Thai being dissolved". While Thais typically refer to her as a princess, Ubolratana in her Instagram post said she would be taking part in the election as a commoner.
Ubolratana, 67, completed her undergraduate and graduate degrees from the the Massachusetts Institute of Technology and the University of California, Los Angeles, respectively. In terms of the outcome, while Prayut was seen as being the likely victor by far in upcoming polls, the most likely scenario now is a unity, royal-led government with Ubolratana at the helm, with Thaksin's influence at play and some role for Prayut-linked forces as well. Friday was the last day for hopefuls to declare their candidacy.
"Even though she relinquished her title according to royal laws. she still retains her status and position as a member of the Chakri dynasty", the king's order said.
The princess has a heavier media presence than any of her siblings, ranging from appearances in Thai movies and television to an Instagram page with about 100,000 followers.