Trimethyl orthoformate (TMOF: HC(OCH3)3) has recently been examined as a viable biofuel. TMOF is a branched isomer of oxymethylene ether-2 (OME2) that, due to its high oxygen content and lack of direct carbon-carbon bonds, considerably reduces the formation of soot particles. To meet the challenges of a more flexible and sustainable power generation, a detailed understanding of its combustion properties is essential for its safe and efficient utilization, neat or in blends. In this work, two fundamental combustion properties of TMOF were studied: (i) Auto-ignition of TMOF/synthetic air mixtures (φ = 1.0; diluted 1:5 with N2) using the shock tube method at pressures of 1, 4, and 16 bar, and (ii) Laminar burning velocities of TMOF/air mixtures using the cone angle method at ambient and elevated pressures of 3 and 6 bar. Furthermore, the impact of TMOF addition to a gasoline surrogate (PRF90) on ignition delay times was studied using the shock tube method at φ = 1.0, 1:5 dilution with N2, T = 900–2000 K, and at 4 bar. The experimental data sets have been compared with predictions of the in-house chemical kinetic reaction mechanism (DLR concise mechanism) developed for interpreting the high-temperature combustion of a broad spectrum of different hydrocarbon fuels as well as oxygenated fuels, including TMOF. The results demonstrate that the ignition delay times of TMOF and OME2 are nearly identical for all pressures studied in the moderate-to high-temperature region. The results obtained for the blend indicate that ignition delay times of the TMOF/PRF90 blend are shorter than those of the primary reference fuel 90 (PRF90) at 4 bar. In the lean-to stoichiometric region, the results obtained for laminar burning velocities of TMOF and OME2 are similar. However, in the fuel-rich domain (φ > 1.0), laminar burning velocities for TMOF are noticeably lower, indicating a decreased reactivity. The model predictions based on the in-house model reveal a good agreement compared to the measured data within the experimental uncertainty ranges. In addition, sensitivity analyses regarding ignition delay times and laminar flame speeds were performed to better understand TMOF oxidation.