Longitudinal ventilation and smoke extraction by shaft are common smoke control methods in road tunnel fires. Tunnels often adopt one of these methods in practical engineering. However, it may have a better effect to adopt the method of mixing the two smoke exhaust methods together, which has not been revealed in the previous literature. Hence, the coupled effects of longitudinal ventilation and natural ventilation with shafts on the smoke control in tunnel fires were studied in this work. Numerical simulation was carried out considering different longitudinal ventilation velocities (0–4 m/s) and 4 kinds of typical shaft arrangements (shaft lengths range of 3–12 m, shaft intervals range of 27–60 m). The smoke spread length and smoke exhaust efficiency were analyzed systematically. Results show that (1) with the increase in longitudinal ventilation velocity, the total smoke spread length firstly decreases (V < 1 m/s) and then keeps almost constant (1 m/s < V < 2 m/s), finally increasing significantly (V > 2 m/s). (2) The length of the dangerous area (over 60 °C) at human height is basically 0 for all cases (except for Scenario 4 of shaft arrangement) when the longitudinal ventilation velocity is less than 2 m/s. (3) The CO smoke flow rate through the shaft is relatively high when the longitudinal ventilation velocity is within the range of 1–2 m/s for 4 kinds of shaft arrangement scenarios. Factors such as smoke spread and smoke exhausted through the shaft are comprehensively considered to judge smoke exhaust performance. The following conclusions can be drawn: when the ventilation velocity ranges from 1–2 m/s, it has a positive impact on the smoke control in tunnel fires with natural ventilation with shafts. When the ventilation velocity exceeds 2 m/s, the total smoke spread length and the length of the danger area increase, and the smoke stratification becomes worse, which brings inconvenience to rescue work. The results can provide reference for the design of fire protection in tunnels.