An exhaust control system for use with a combustion engine having a reduction catalyst and a supply of reductant is disclosed. The exhaust control system may have a first sensor located to generate a first signal indicative of an amount of a constituent within the exhaust entering the reduction catalyst, a second sensor located to generate a second signal indicative of an amount of the constituent remaining within the exhaust exiting the reduction catalyst, and a third sensor configured to generate a third signal indicative of an amount of reductant within the supply. The exhaust control system may additionally have a controller in communication with the first sensor, the second sensor, and the third sensor. The controller may be configured to determine a change in an efficiency of the reduction catalyst based on the first and second signals, and diagnose the change in efficiency based on the third signal.