After the election of 1977 Kroes was appointed as State Secretary for Transport and Water Management in the Cabinet Van Agt–Wiegel taking office on 28 December 1977.

In October 2004, Kroes was nominated as the next European Commissioner in the First Barroso Commission, and was given the heavy portfolio of Competition taking office on 22 November 2004.

After her ministerial career, Kroes spent two years working on two projects as an advisor to Karel van Miert, at that time European Commissioner for Transport.

Until 2004 Kroes maintained an office in the castle of Jan-Dirk Paarlberg, a real estate mogul who was convicted to four and a half years in prison for money-laundering and extortion.

At the time, her nomination was heavily criticised because of her ties to big business and alleged involvement in shady arms deals.

Kroes has tried to uphold her integrity; whenever she has to deal with issues concerning competition in branches of industry in which she used to be active as a board member, Commissioner McCreevy takes over her responsibilities.

This case resulted in the requirement to release documents to aid commercial interoperability and included a €497 million fine for Microsoft.

In December 2011, Kroes invited Karl-Theodor zu Guttenberg who had resigned as German Minister of Defence in March 2011, due to plagiarism charges – as advisor to the European Commission as part of its No Disconnect Strategy designed to promote Internet freedom.

[12] In November 2012, Kroes made international news when she said her advisers at the Internet Governance Forum in Baku, Azerbaijan had been the victims of computer hacking.

[16] As Minister of Transport, Public Works and Water Management, Kroes had conceived the plan to provide subsidies to the companies TCA and TCR (Tanker Cleaning Amsterdam and Rotterdam, respectively).

Even though she was made aware of the company's criminal activities, including mixing chemical waste into fuel oil, she pushed through with the subsidies.

Kroes was accused by the investigative committee that she had helped a rogue company with a government subsidy into the saddle, which made the environmental crimes possible.

As chairman of a consortium of Holland Signaal, Ballast Nedam and Koninklijke Schelde (supported by the navy, the Port of Rotterdam Authority and the Dutch Ministry of Economic Affairs), Kroes attempted to exchange the frigates for oil supplies.

When it turned out that she was also using her chairmanship to serve the business interests of a personal friend, the businessman Joop van Caldenborgh, she was removed from her position by the government.

The frigate affair brought Kroes into contact with Jordanian investor Amin Badr-El-Din, with whom she would run the company Mint Holdings some years later, which was planning to take over part of Enron.

She did not disclose the numerous appointments she had with firms executives when European Commissioner for competition and then new technologies (a position she held until November 2014).

After resigning from the European Commission, she actively helped Uber bending regulations by opening her contacts to the company, including Netherlands then Prime Minister Mark Rutte, breaking her 18-months duty of réserve that ex commissioner must apply.

She is a confidant of Ayaan Hirsi Ali, known for her criticism of Islam and having a fatwa issued, and persuaded her to switch allegiance from the social democratic PvdA to the VVD.