We introduce a global analysis of collinearly factorized nuclear parton distribution functions (PDFs) including, for the first time, data constraints from LHC proton–lead collisions. In comparison to our previous analysis, EPS09, where data only from charged-lepton–nucleus deep inelastic scattering (DIS), Drell–Yan (DY) dilepton production in proton–nucleus collisions and inclusive pion production in deuteron–nucleus collisions were the input, we now increase the variety of data constraints to cover also neutrino–nucleus DIS and low-mass DY production in pion–nucleus collisions. The new LHC data significantly extend the kinematic reach of the data constraints. We now allow much more freedom for the flavor dependence of nuclear effects than in other currently available analyses. As a result, especially the uncertainty estimates are more objective flavor by flavor. The neutrino DIS plays a pivotal role in obtaining a mutually consistent behavior for both up and down valence quarks, and the LHC dijet data clearly constrain gluons at large momentum fraction. Mainly for insufficient statistics, the pion–nucleus DY and heavy-gauge-boson production in proton–lead collisions impose less visible constraints. The outcome – a new set of next-to-leading order nuclear PDFs called EPPS16 – is made available for applications in high-energy nuclear collisions.