The European Union (EU)—the world’s most advanced and exemplary case of regional integration—is adapting to an era when internal criticisms are becoming more influential than ever before in the history of European integration. An entirely new party family of Eurosceptic parties has emerged and consolidated over the last decade. Given that one of their main aims is to challenge and critique the EU, Eurosceptic parties have a particular interest in European issues—the European polity as well as major European policies. Against this backdrop, the paper investigates whether and how the rise and consolidation of Eurosceptic parties of the left and right has affected party competition over European polity and policy issues. Empirically, we use information from the Euromanifesto data set covering the past 40 years (1979–2019) relating to elections to the European Parliament. Our paper’s findings suggest that the upsurge and consolidation of Eurosceptic parties of the left and right has an important effect on party competition over European issues: Eurosceptic party success affects mainstream leftist parties’ issue salience and position when it comes to the EU polity. Moreover, higher levels of support for far-right Eurosceptic parties have an impact on the position of rightist mainstream parties on EU cultural policy issues, whereas leftist mainstream parties appear mostly unresponsive to the Eurosceptic parties’ success when it comes to EU economic policy issues. These findings give us a clearer insight on how exactly Eurosceptic parties are transforming mainstream party competition.