We present the first cosmology results from large-scale structure using the full 5000 deg2 of imaging data from the Dark Energy Survey (DES) Data Release 1. We perform an analysis of large-scale structure combining three two-point correlation functions (3 ×2 pt ): (i) cosmic shear using 100 million source galaxies, (ii) galaxy clustering, and (iii) the cross-correlation of source galaxy shear with lens galaxy positions, galaxy-galaxy lensing. To achieve the cosmological precision enabled by these measurements has required updates to nearly every part of the analysis from DES Year 1, including the use of two independent galaxy clustering samples, modeling advances, and several novel improvements in the calibration of gravitational shear and photometric redshift inference. The analysis was performed under strict conditions to mitigate confirmation or observer bias; we describe specific changes made to the lens galaxy sample following unblinding of the results and tests of the robustness of our results to this decision. We model the data within the flat Λ CDM and w CDM cosmological models, marginalizing over 25 nuisance parameters. We find consistent cosmological results between the three two-point correlation functions; their combination yields clustering amplitude S8=0.77 6-0.017+0.017 and matter density Ωm=0.33 9-0.031+0.032 in Λ CDM , mean with 68% confidence limits; S8=0.77 5-0.024+0.026, Ωm=0.35 2-0.041+0.035, and dark energy equation-of-state parameter w =-0.9 8-0.20+0.32 in w CDM . These constraints correspond to an improvement in signal-to-noise of the DES Year 3 3 ×2 pt data relative to DES Year 1 by a factor of 2.1, about 20% more than expected from the increase in observing area alone. This combination of DES data is consistent with the prediction of the model favored by the Planck 2018 cosmic microwave background (CMB) primary anisotropy data, which is quantified with a probability-to-exceed p =0.13 -0.48. We find better agreement between DES 3 ×2 pt and Planck than in DES Y1, despite the significantly improved precision of both. When combining DES 3 ×2 pt data with available baryon acoustic oscillation, redshift-space distortion, and type Ia supernovae data, we find p =0.34 . Combining all of these datasets with Planck CMB lensing yields joint parameter constraints of S8=0.81 2-0.008+0.008, Ωm=0.30 6-0.005+0.004, h =0.68 0-0.003+0.004, and ∑mν<0.13 eV (95% C.L.) in Λ CDM ; S8=0.81 2-0.008+0.008, Ωm=0.30 2-0.006+0.006, h =0.68 7-0.007+0.006, and w =-1.03 1-0.027+0.030 in w CDM .