[2] In September 2018, Weber declared his intention to run for the position of President of the European Commission[3] and was elected as the Spitzenkandidat of the EPP in November.

[5][6] It was announced on 28 May that the new European Commission President would be picked at an EU summit in June; Weber was not nominated, with Ursula von der Leyen selected instead.

In 2015, Bavaria's Minister President Horst Seehofer nominated Weber as one of his deputies in the office of CSU chairman, making him part of the party's leadership.

In the negotiations to form a coalition government under the leadership of Chancellor Angela Merkel following the 2017 federal elections, he was part of the working group on European policy, led by Peter Altmaier, Alexander Dobrindt and Achim Post.

Also, he told The Guardian in early 2015 that the United Kingdom's drive to freeze welfare payments for EU immigrants was justified and set an example for the rest of the union.

[20] In July 2013, when the European Parliament Committee on Civil Liberties, Justice and Home Affairs (LIBE) issued the Tavares Report criticizing the erosion of fundamental rights in Hungary, Weber dismissed it as a politically motivated attack on the government of Hungarian Prime Minister Viktor Orbán by leftist parties.

[21] However, in September 2018 he approved the Sargentini report voting to trigger Article 7 of the Treaty on European Union procedure against the government of Hungarian Prime Minister Viktor Orbán.

Rather than new supplies across the Baltic, Weber called upon the commission to accelerate its efforts to import more gas across Turkey from the Caspian Sea, and even potentially Iran and Iraq.

[28] In response to the arrest and detention of Alexey Navalny in early 2021, Weber demanded that the EU cut financial transactions from President Vladimir Putin's inner circle.

[29] In March 2018, Weber voted against initiatives prohibiting gay conversion therapies, unlike the majority of the European People Party's MEPs.

[30] In April 2023, the Regional Government of Andalusia, led by the conservative People's Party, proposed a law to legalise to date illegal extraction of water for irrigation in the Doñana National Park, home to one of Europe's largest wetlands and UNESCO World Heritage, threatened by drought.

[32] Weber disagreed on this stance, accusing the von der Leyen Commission of playing "party politics" and of campaigning against the regional Government of Andalucía and in favour of Spanish Socialist Prime Minister Pedro Sánchez.

[33] Incumbent European Commissioner for Environment, Oceans and Fisheries Virginijus Sinkevičius contradicted Weber pointing out, that "Doñana is important for Spain & the EU".