Meta has been handed a €798m (£664m) fine for breaking competition law by integrating Facebook Marketplace within its social network.
This meant alternative classified ads services faced "unfair trading conditions", the commission said, making it harder for them to compete.
The company will also be ordered to stop imposing these conditions on other services.
Meta said that it rejected the Commission's findings and that it would appeal.
As for the EU's case, it has the subject antitrust chief herself, Margrethe Vestager, stating that Facebook fettered the development of other online classified ads service providers.
"It did so to benefit its own service Facebook Marketplace, thereby giving it advantages that other online classified ads service providers could not match," she added,
She said Meta "must stop this behavior", while the EU asked the firm to "refrain from repeating" the infringement.
Meta said the Commission had provided "no evidence" of harm either to competitors or consumers.
"This decision ignores the market realities, and will only serve to protect incumbent marketplaces from competition. "
The ruling is the result of an investigation which the Commission opened in 2021, after Meta's rivals complained that Facebook Marketplace gave it an unfair advantage.
Fine, fine, fine
Meta has not received a fine by the EU as a result of breaking competition rules, though it was ordered to pay €110m back in 2017 after not providing sufficient information when purchasing WhatsApp.
The Irish Data Protection Commissioner also fined Meta over €1bn on account of mishandling peoples' data while transferring it from Europe to the United States beforehand.
It also had to pay a relatively small £50m in 2021 when the UK's Competition and Markets Authority accused it of intentionally breaching rules over its bid to take over GIF-maker Giphy and demanded that it sell the company entirely.
The move comes as regulators around the world are getting tougher on tech giants, with the US government even mulling a break-up of Google.