Andrei Nastase’s career began at the Transportation Prosecution Office in Chisinau. He also worked as a legal director at the Moldovan-German venture Air Moldova. From 2002 till 2015 he worked as a lawyer and defended the interests of the German company Unistar and of business people Viorel Topa and Victor Topa (not related), who had been sentenced by a Moldovan court for blackmail, fraud, money laundering, and forgery of official papers.

In 2015 Mr. Nastase founded the Dignity and Truth Platform (DA), which later has been transformed into a political party. In 2016 he announced plans to run for the president of Moldova but then changed his mind and let his ally Maia Sandu of the Action and Solidarity Party (PAS) come forward as the candidate of both opposition parties.

In 2018 Andrei Nastase came victor in the election for the mayoralty of the capital but never could take the seat because a court of law refused to validate the results of the local elections. The judge found that a video Mr. Nastase shared on social media on the election day was a major influencer among voters.

In the February 2019 parliamentary elections, he competes in the constituency №33 - Chisinau, where he won a majority. However, he leaves the Parliament months later in order to serve as a deputy prime minister and minister of internal affairs.

At the 1 November 2020 presidential elections Andrei Nastase is the candidate of the Dignity and Truth Party, obtaining in the first round 3.26% of the votes.

At the parliamentary elections in July 2021, he was the top candidate, but the Dignity and Truth Platform received only 34,184 votes, or 2.3% of the total, and did not enter Parliament. At the end of 2021, he stepped down from the leadership of the Dignity and Truth Platform. In 2022, he left the Platform following accusations that he voted in the Chisinau Municipal Council for the privatization of certain properties.

Andrei Nastase is running in the presidential elections on 20 October 2024 as an independent candidate.