Considering the fact that people spend most of their time indoors it is important to maintain good indoor environment for human health, comfort and performance. Current ventilation control strategies do not consider presence of multiple contaminants and fail to maintain the required indoor air quality (IAQ) in times where indoor and outdoor contaminant sources are strong. In this paper, a ventilation strategy that is based on control of concentration levels of critical contaminants as well as overall IAQ is proposed. The strategy considers multiple contaminants of concern from indoor and/or outdoor sources. When outdoor contaminant level exceeds a value that has a potential to exceed indoor permissible level at steady state, outdoor air damper is kept at minimum position based on ASHRAE 62.1 standard. Otherwise, the contaminant concentration in the critical zone (the zone with maximum contaminant concentration difference above the permissible level) is used to set the outdoor air damper’s minimum position. For conditions that do not need minimum damper position, split range sequencing control strategy is used. To evaluate performance of the proposed strategy on IAQ and energy, a SIMULINK model has been developed for a five zone sample building with VAV. Four contaminants were selected for this study: Toluene, Formaldehyde, PM2.5 and CO2. The model is simulated for one year period for different locations representing different outdoor climate and pollution conditions. The performance of the building with the new control strategy was compared against two baseline ventilation systems, one defined per ASHRAE 62.1 with no demand control and the other with 30% more ventilation rate per the USGBC’s LEED standard for green building certification. For the specific buildings and climates studied, the proposed strategy resulted in an average energy saving of 22% and 32% compared to the two baselines, respectively. Most importantly, the IAQ was maintained in its permissible range for the entire year simulated.