The plan, launched on Thursday by the Commission, includes guidelines to promote the prudent use of antimicrobials in people and animals.
The guidelines target doctors, nurses, pharmacists, hospital administrators and others who play a role in antimicrobial use.
They complement infection prevention and control guidelines which may exist at national level.
The plan includes more than 75 actions based on three main pillars.
First, making the EU a best-practice region - this, said the Commission, will require better evidence, coordination and surveillance and improved control measures.
Second, boosting research, development and innovation - the Commission said it will work in partnerships with member states and industry, including SMEs, to address AMR in bacteria, fungi and parasites. Special attention will be given to the WHO priority list of pathogens as well as tuberculosis, HIV/AIDS, malaria and neglected infectious diseases.
Third, shaping the global agenda - whereas areas of action have been agreed upon internationally, the EU will work towards reinforcing engagement and collaboration with multilateral organisations, and intensifying cooperation with the most affected developing countries.
The new initiative seeks to build on the first AMR action plan, which ran from 2011 to 2016.
A conference in Parliament this week heard that AMR is as big a threat to society as climate change.
Portuguese MEP José Inácio Faria has welcomed the adoption of the new action plan; AMR is a growing threat that is responsible for 25,000 deaths and a €1.5bn loss in the EU every year.
Faria, an EPP group MEP, said that given the rising death toll, the move was of "paramount importance" in tackling AMR which, it is estimated, will claim the lives of up to 10 million people by 2050.
He said, "The truth is that resistant bacteria do not respect borders."
Further comment came from Vytenis Andriukaitis, Commissioner for health and food safety, who said, "AMR is a global growing threat, and if we do not step up our action and commitment now, by 2050 it could cause more deaths than cancer."
He added, "This ambitious agenda focuses actions on key areas with the highest added value for EU countries. By promoting prudent use of antimicrobials in people and animals, consolidating surveillance, improving data collection and boosting research, I aim to make the EU a best practice region worthy of shaping the global agenda on AMR in this increasingly interconnected world."
Elsewhere, Carlos Moedas, Commissioner for research, science and innovation, said, "AMR already kills thousands and is a significant burden for the society and the economy. It's a threat that no country can tackle alone. We need a truly European research effort to save human lives, animals and the environment."
He added, "That's why the action plan is so important - it will mean better research coordination and collaboration between EU member states, as well as public and private sectors across Europe and beyond".
The action plan, said the Commission, is underpinned by a 'One Health' approach that addresses resistance in both humans and animals.