On 16 January 2018, Babiš's cabinet lost a vote of no confidence by 117 votes to 78.
In February 2018, his cabinet approved the European Fiscal Compact and sent it to the Chamber of Deputies for further approval. They also proposed changes to the Civil Service Act, which has been the subject of controversy since it was passed in 2015 by Bohuslav Sobotka's government, in which Babiš served as Minister of Finance.
On 6 June 2018, President Zeman appointed Andrej Babiš as Prime Minister for the second time, calling on him to present him with a proposed list of members of the government. Babiš was sworn in by President Zeman for the second time on 27 June 2018, as the head of a minority government formed from ANO and CSSD representatives. Zeman refused to appoint CSSD deputy and MEP Miroslav Poche as Minister of Foreign Affairs, so he was replaced by CSSD party chairman and Interior Minister Jan Hamacek. CSSD took five seats in the government, and ANO took ten. On 10 July the two parties signed a coalition agreement. Taťána Malá was appointed Minister of Justice for ANO, but resigned 13 days later following allegations of plagiarism in her diploma theses and conflict of interest. Babiš briefly considered consulting with Zeman about the choice for a replacement minister, but in the face of vigorous opposition from opposition parties, he instead nominated Jan Kněžínek, who was sworn in by Zeman on 10 July. On 12 July 2018, shortly after midnight, Babiš's government won a confidence vote in the Chamber of Deputies by a vote of 105–91, with the external support of the Communist Party of Bohemia and Moravia.
In March 2018, Babiš ordered three Russian diplomats to leave the country in a show of solidarity with the United Kingdom after a former Russian double agent Sergei Skripal was poisoned in Salisbury.
In June 2018, German Chancellor Angela Merkel said that there had been "no moral or political justification" for the post-war expulsion of ethnic Germans from Czechoslovakia. Babiš responded: "I reject this characterisation – especially when we recall the horrors of Heydrich, Lidice, Ležáky and the killing of our paratroopers. I have the feeling that there is some internal political struggle in Germany now, and it is very unfortunate that old wounds are opening because of it."
On 11 November 2018, Babiš represented the Czech Republic in a ceremony at the Arc de Triomphe in Paris to celebrate the 100th anniversary of the end of the First World War. The ceremony was attended by world leaders including US President Donald Trump, German Chancellor Angela Merkel and Russian President Vladimir Putin.
In mid-November 2018, investigative journalists Sabina Slonková and Jiří Kubík published an interview with Babiš's son, who they had tracked down in Switzerland. Andrej Babiš Jr told the journalists that after the beginning of the Stork Nest affair he was taken to the Crimea, where he was subsequently detained against his will. He also stated that he had signed documents for his father without knowing what they were. Babiš responded that his son was mentally ill, taking medication and required supervision, and that he had left the Czech Republic voluntarily.
In response to the story, the opposition called on Babiš to resign on 13 November 2018. On 15 November 2018, the Senate adopted a resolution that Babiš was unacceptable in the government while the investigation into the Stork's Nest case was continuing, but the same day President Zeman stated that if the Chamber of Deputies voted the government down, he would again ask Babiš to form a new cabinet. On 16 November 2018, Babiš stated that he would not resign. On 23 November 2018, Babiš and his government survived a vote of no confidence, as the communists voted with the government and CSSD deputies left the chamber.
In November 2018, Seznam News television aired an interview with Babiš' son Andrej Babiš Junior (born 1982) in which he alleged that he had been kidnapped by an associate of his father to obstruct the corruption inquiry relating to the Stork's Nest Farm. Babiš Junior was quoted as saying he had been held in Crimea, Kaliningrad, Moscow and Kryvyi Rih in Ukraine, to stop him from giving a statement to the police about his involvement in the case. Prime Minister Babiš denied the kidnapping, but admitted that his son had entered Crimea, among others, also saying that his son suffers from schizophrenia.