Isothermal treatment affects the microstructural evolution and the precipitation behavior of high-strength low alloy (HSLA) steels. In this regard, thermal simulation of different isothermal treatment temperatures was adopted by using a thermomechanical simulator. The results showed that hardness reached the maximum value at 600 °C holding temperature, which was related to a finer grain structure and granular bainite. The strengthening effect of precipitates was remarkable due to the combination of small particle size and small interparticle spacing. It is presumed that the precipitation started after 600 s at 600 °C. Precipitation strengthening continued to exist, even though coarsening of ferrite grains led to softening phenomena when the specimen was isothermally held at 750 °C, which led to relatively high hardness. The precipitates were fcc (Ti, Nb) (N, C) particles, and belonged to MX-type precipitates. Average size of precipitates increased from 3.14 to 4.83 nm when the specimens were isothermally held between 600 °C and 800 °C. Interparticle spacing of precipitates also increased with increasing isothermal treatment temperatures. These led to a reduction in precipitation strengthening. At the same time the polygonal ferrite content increased and ferrite grain size got larger, such that the hardness decreased continuously.