The paper presents new parton distribution functions (PDFs) of the proton derived from a global analysis of hard scattering data in the framework of perturbative quantum chromodynamics (QCD). The analysis includes recent theoretical developments and collider data from deep-inelastic scattering (DIS), vector boson production, and single-inclusive jet production. Due to the disagreement between D0 Run-II W lepton asymmetry data and some fixed-target DIS data, two sets of PDFs, CT10 and CT10W, are presented, with and without these high-luminosity W lepton asymmetry data, respectively. The paper discusses the impact of these data on the PDFs and their uncertainties, and studies theoretical predictions and uncertainties for various processes at the Fermilab Tevatron and the CERN Large Hadron Collider (LHC). The analysis introduces several new features, including the treatment of normalization uncertainties, a more flexible PDF parametrization, and a new $\chi^2$ measure of consistency. The paper also examines the quality of fits to individual data sets and provides detailed comparisons with previous data sets, such as HERA-1 DIS data. The results show that the new PDFs have significant implications for observables sensitive to the down-up quark ratio, such as jet pair production, electroweak and Higgs boson production, and processes beyond the Standard Model.The paper presents new parton distribution functions (PDFs) of the proton derived from a global analysis of hard scattering data in the framework of perturbative quantum chromodynamics (QCD). The analysis includes recent theoretical developments and collider data from deep-inelastic scattering (DIS), vector boson production, and single-inclusive jet production. Due to the disagreement between D0 Run-II W lepton asymmetry data and some fixed-target DIS data, two sets of PDFs, CT10 and CT10W, are presented, with and without these high-luminosity W lepton asymmetry data, respectively. The paper discusses the impact of these data on the PDFs and their uncertainties, and studies theoretical predictions and uncertainties for various processes at the Fermilab Tevatron and the CERN Large Hadron Collider (LHC). The analysis introduces several new features, including the treatment of normalization uncertainties, a more flexible PDF parametrization, and a new $\chi^2$ measure of consistency. The paper also examines the quality of fits to individual data sets and provides detailed comparisons with previous data sets, such as HERA-1 DIS data. The results show that the new PDFs have significant implications for observables sensitive to the down-up quark ratio, such as jet pair production, electroweak and Higgs boson production, and processes beyond the Standard Model.