LUXEMBOURG—Alphabet unit Google lost an appeal to a 2.42-billion-euro ($2.8-billion) European antitrust decision on Wednesday, a major win for the bloc’s competition chief Margrethe Vestager in the first of three court rulings that will strengthen the EU’s push to regulate Big Tech. Vestager sanctioned the world’s most popular Internet search engine in 2017 for favoring its own price-comparison shopping service to give it an unfair advantage against smaller European rivals. The shopping case was the first of a trio of decisions that has seen Google rack up a total of 8.25 billion euros in EU antitrust fines in the last decade. The company could face yet more defeats in the other two cases involving its Android mobile operating system and AdSense advertising service, where the EU is seen to have stronger arguments. The court ruling will strengthen Vestager’s hand in her investigations into Amazon, Apple, and Facebook. “The General Court …