Unscrew the registers, then distinguish the supply vents from the return vents by holding a tissue near each vent. The tissue will blow outward if it’s a supply vent.
Cover the supply vents with paper towels or plastic, and hold them in place with the register to prevent dust from escaping into your home as you're cleaning.
Shut down the heating and cooling system and set the thermostat to fan-only or heat mode. The fan will blow dust to where you blocked the supply registers.
Using a flashlight to see, start with the uncovered air return vents, brushing the debris from inside the ducts and tapping the brush handle against the sides of the ducts.
Use a wet-dry vacuum or a regular vacuum’s hose attachment to remove any accumulated debris, like pet fur, from the return vents. Slide it into the vent as far as possible.
Then, remove the paper towel from the supply vents, vacuum them, and re-cover them. You can also use a damp rag to wipe inside the vents on both ends to remove stubborn dust.
To remove mold, prevent future growth, and alleviate odors, use a HEPA vacuum and an antimicrobial spray. Wear protective gear to avoid exposure to mold spores.