[4] Jetten began his political career as a policy advisor for the D66 faction in the Senate of the States General and as the chairman of the Young Democrats.

[8] He succeeded Sigrid Kaag after she announced that she would not lead D66 into the 2023 general election, due to the impact of the "hate, intimidation and threats" she receives on her family.

[15] When that cabinet presented its 2025 budget which included €2 billion in education cuts, Jetten formed the self-named "unholy alliance" with centrist and conservative opposition parties.

Coalition parties needed additional support in the Senate, but D66 pulled out of negotiations in early December 2024, a week before an agreement was reached to reverse €750 million of the cuts.

[16][17] During the Russian invasion of Ukraine, he advocated for Dutch defense spending to rise from 2% to 3% of gross domestic product, believing that Europe could no longer rely on the United States for its security following the second inauguration of US president Donald Trump in 2025.