Close the damper on your fireplace. This alone isn't enough, but it's a necessary first step.
Disconnect the fireplace from the chimney with a fireplace balloon. Also called a fireplace plug or a fireplace pillow, this tool is temporary, making it ideal for seasonal fireplace closings. Inflate the balloon partially and insert it into the chimney through the fireplace, then inflate it the rest of the way to form a tight seal.
Create a seal around the fireplace with a piece of insulation board. Cut the board with a razor so that it is larger than the fireplace opening but not larger than the mantle around it. Press the board into place, then seal it in place by caulking it against the mantle. If caulk doesn't adhere to your mantle, simply seal the board in place with duct tape.
Seal the joint where your chimney and fireplace mantle meet the wall with caulk. This prevents air leaks.