A method for controlling a downhole pressure during drilling comprises continually sensing in real-time at least one real-time fluid property of an input fluid to a well and of a return fluid from the well. A wellhead setpoint pressure is calculated in real-time that results in a predetermined downhole pressure at a predetermined location in the well, where the calculation based, at least in part, on the at least one continually sensed real-time fluid property. The flow of the return fluid is controllably regulated to maintain the calculated wellhead setpoint pressure.