A new generation of parton distribution functions (PDFs) with increased precision and quantitative estimates of uncertainties is presented. This work extends previous CTEQ and other global analyses in two key areas: (i) a full treatment of experimental correlated systematic errors for new and old data sets; and (ii) a systematic and pragmatic treatment of uncertainties using an eigenvector-basis approach to the Hessian method. The new gluon distribution is significantly harder than previous fits. The paper presents extensive results on uncertainties of PDFs at various scales and parton luminosity functions at the Tevatron Run II and LHC. It estimates uncertainties for W and Z production cross sections at the Tevatron and LHC as ±4% and ±5%, respectively, and for a light Higgs at the LHC as ±5%. The paper describes new experimental data sets and methodologies, including the treatment of correlated systematic errors and the use of the Hessian method. It presents results on new PDFs, including the "standard" CTEQ6 sets and eigenvector sets for uncertainty analyses. It discusses physics issues, such as the behavior of the gluon distribution, and provides a user interface for accessing the results. The paper also compares the new results with previous studies and discusses the impact of higher-twist effects and the determination of the strong coupling constant αs. The results show improved fits to experimental data, with the new PDFs providing a more accurate description of parton distributions. The uncertainties in the PDFs are quantified, and the results are compared with other PDF analyses. The paper concludes with a discussion of the implications of the results for future physics studies.A new generation of parton distribution functions (PDFs) with increased precision and quantitative estimates of uncertainties is presented. This work extends previous CTEQ and other global analyses in two key areas: (i) a full treatment of experimental correlated systematic errors for new and old data sets; and (ii) a systematic and pragmatic treatment of uncertainties using an eigenvector-basis approach to the Hessian method. The new gluon distribution is significantly harder than previous fits. The paper presents extensive results on uncertainties of PDFs at various scales and parton luminosity functions at the Tevatron Run II and LHC. It estimates uncertainties for W and Z production cross sections at the Tevatron and LHC as ±4% and ±5%, respectively, and for a light Higgs at the LHC as ±5%. The paper describes new experimental data sets and methodologies, including the treatment of correlated systematic errors and the use of the Hessian method. It presents results on new PDFs, including the "standard" CTEQ6 sets and eigenvector sets for uncertainty analyses. It discusses physics issues, such as the behavior of the gluon distribution, and provides a user interface for accessing the results. The paper also compares the new results with previous studies and discusses the impact of higher-twist effects and the determination of the strong coupling constant αs. The results show improved fits to experimental data, with the new PDFs providing a more accurate description of parton distributions. The uncertainties in the PDFs are quantified, and the results are compared with other PDF analyses. The paper concludes with a discussion of the implications of the results for future physics studies.