1,3-Butadiene is the simplest conjugated diene, which is widely used in polymer materials, organic synthesis, and other fields. The investigation of its thermal stability and oxidation characteristics is necessary for production, transportation, and use safety. The pressure and temperature behavior of the autoxidation reaction of 1,3-butadiene with oxygen were determined using a custom-designed mini closed pressure vessel test (MCPVT). The effects of free radical initiators CHP and AIBN on the oxidation reaction were investigated. The thermal decomposition characteristics of oxidation products were measured by differential scanning calorimetry (DSC), and its hazards were discussed. The results showed that the oxidation reaction of 1,3-butadiene was easy to occur. Moreover, the activation energies of autoxidation, CHP-initiated oxidation, and AIBN-initiated oxidation reaction were 20.85 kJ·mol−1, 33.30 kJ·mol−1, and 56.27 kJ·mol−1, respectively. In addition, the oxidation products were analyzed by headspace sampler-gas chromatography-mass spectrometry (HS-GC–MS), GC–MS, and iodometry. Some of 1,3-butadiene oxidation products under three conditions are the same, for example, 3-butene-1,2-diol, 4-vinylcyclohexene, 2(5H)-furanone, 2-propen-1-ol, and 2,6-cyclooctadien-1-ol. According to the reaction products, the oxidation reaction pathway of 1,3-butadiene was described. The research results are significant for avoiding fire and explosion accidents in the production, transportation, and application of 1,3-butadiene.