She remained in the tax division until being nominated to serve as finance minister in 2009, tasked with stimulating the Lithuanian economy in the aftermath of the Great Recession.

Šimonytė returned to politics in 2016, when she ran as an independent candidate in the 2016 parliamentary election to represent Antakalnis constituency in Vilnius, ultimately winning a seat in parliament.

Following the certification of the election results, Šimonytė was proposed as the prime ministerial candidate by a coalition consisting of the Homeland Union, Liberal Movement and Freedom Party; she took office on 11 December, along with the appointment of her cabinet.

[4] In 1997, Šimonytė first began working professionally as an economist and public servant, after being hired at the Ministry of Finance within its tax division.

Upon taking office, Šimonytė was tasked with recovering the Lithuanian economy in the aftermath of the Great Recession, with Lithuania's gross domestic product (GDP) having dipped 14.7% in 2009.

[8] In 2015, Šimonytė planned her return to politics after confirming her intention to stand as a candidate in the 2016 parliamentary election, aiming to represent the Antakalnis constituency within Vilnius.

[16][17] Following the 2019 presidential election, Šimonytė had emerged as an unofficial leader of the Homeland Union and one of the most prominent politicians affiliated with the party, despite being officially an independent.

[20][21] On 9 November, the coalition agreement was signed between the Homeland Union, Liberal Movement, and Freedom Party, paving the way for Šimonytė to become prime minister.

[23] Šimonytė was appointed prime minister on 11 December 2020 by President Gitanas Nausėda,[24] becoming the second woman to serve in the role, following Kazimira Prunskienė.

[28] The government of Saulius Skvernelis held its last meeting on 9 December 2020, before the new cabinet is expected to assume office on Friday.

[30] From 15 February, partial lifting of lockdown was made, including decision to re-open small shops and beauty salons.

[31] On 22 March 2021, Šimonytė, Speaker of the Seimas Viktorija Čmilytė-Nielsen, and Health Minister Arūnas Dulkys also received the same vaccine.

During the meeting, the prime minister said:[35] <...> Release of political prisoners, end of repression, and free and democratic elections are the key steps that Belarusians are demanding.

[36] In an October 2022 interview with Nikkei Asia, she stated that Lithuania's ties with Taiwan can contribute to significant development in industrial fields such as semiconductors and lasers.

"[87] Šimonytė supports scientific data on climate change, and referred to Donald Trump's decision to withdraw from the Paris Agreement as a "mistake".

[86] Šimonytė’s new ruling coalition has agreed to defend "those fighting for freedom" in Taiwan, suggesting that Lithuania's relations with China would not be a priority for her government.

[91] Šimonytė has stated that she did not oppose the introduction of same-sex civil unions to Lithuania, which attracted the support of LGBT rights activists.

[4] The Good Soldier Švejk, a satirical dark comedy by Czech writer Jaroslav Hašek, is one of Šimonytė's favorite books, whose characters she has often publicly quoted during her political career.