A powertrain system for a mobile machine is disclosed. The powertrain system may have a power source, a plurality of traction devices, and a differential operatively connecting an output of the power source with the plurality of traction devices. The powertrain may also have a manual input device movable by an operator to generate a first signal indicative of a desire to lock the differential, at least one sensor configured to generate a second signal indicative of a parameter of the mobile machine, and a controller in communication with the at least one sensor, the manual input device, and the differential. The controller may be configured to inhibit locking of the differential based on the first signal when the second signal indicates the parameter deviating from an acceptable range.