This study describes and analyzes measurements of 119 non-polar organic compounds in PM2.5 samples from three urban sites in the Southeastern Aerosol Research and Characterization (SEARCH) network: Jefferson Street in Atlanta, Georgia (JST), Birmingham, Alabama (BHM), and Hinton, Texas (HIN). Daily 24-h PM2.5 samples were collected on quartz-fiber filters from January 2006 through 2007 at HIN and from March 2006 through 2010 at JST and BHM. PM2.5 sampling at BHM and JST is ongoing. The measured species are associated with directly emitted particles and potentially serve as tracers of specific types of emissions. PM2.5 organic measurements include 28 n-alkanes (C15–C42), 18 iso-/anteiso-alkanes (C29–C37), 2 methyl alkanes, 3 branched alkanes, 5 cycloalkanes, 32 PAH compounds, 18 hopanes, 12 steranes, and 1 alkene, many of which are constituents of motor-vehicle exhaust and other anthropogenic PM2.5 emissions. Predominantly anthropogenic origins of the measured compounds are indicated by weekly and seasonal cycles that are identified with known emission patterns, especially for motor vehicle usage. Annual mean concentrations of each class of compounds declined by 60–90% from 2006 through 2009, then increased in 2010 to concentrations comparable to 2008. These changes are similar to 40% reductions of on-road and non-road motor-vehicle exhaust PM2.5 emissions between 2006 and 2010. Year-to-year variations in OC correlated with year-to-year variations in measured non-polar compound concentrations. Regression of OC against the sums of measured n-alkanes, iso-/anteiso-alkanes, PAHs, hopanes, and steranes indicates that 32 ± 7% of OC at BHM and 35 ± 4% of OC at JST derived from sources emitting the measured non-polar compounds. The reductions in measured concentrations of EC, OC, and non-polar OC species represent an important improvement in air quality in the southeastern U.S. that can be attributed by the long-term measurement program to PM2.5 emission reductions.