On a Monday afternoon in May 2019, I will take the National Express from LHR T3 to Cambridge. I can make a reservation, or not. Making a reservation guarantees a seat. Making a reservation for two hours after the flight's scheduled ETA would allow for delays, but isn't appealing as my flight has very good on-time performance. No reservation allows me to take the next available bus...provided there are empty seats.
Are buses on this route often or usually full?
In my experience, this bus is rarely full, and is really very unlikely to be full on a Monday afternoon. One reason for this is that it isn't a particularly cheap or quick way to get to Cambridge (£25, at least 2.5 hours).
Of course there are no guarantees, but in your position I would go without a reservation and see what the bus situation is. In the unlikely event that the bus is full, you could (for about the same cost) take the Piccadilly (London Underground) Line from Heathrow to King's Cross (about 45 mins - 1 hr) and then then train to Cambridge from there (50 mins for a fast service). Depending on how you balance the convenience of not having to travel through London with the duration and discomfort of the bus journey, you might choose to do this anyway.
