Mythbusters visited this topic in both episode 22 and episode 38:
PARTLY CONFIRMED *
Tests were performed under varying conditions (55 mph versus 45 mph). The 55 mph test used a computer to estimate fuel efficiency based on air intake, not actual fuel consumption, and showed A/C was more efficient. The 45 mph test consisted of running the tank until it was empty, and showed open windows were more efficient.
- Because the original tests were inconclusive, this "urban puzzle" was revisited in episode 38: It is more fuel efficient to use air conditioning when the car is traveling approximately 50mph or more. Otherwise, windows are more fuel efficient.
The fundamental flaw in the MythBusters’ test was that the point where the drag becomes powerful enough to inhibit a car’s performance with windows down was inside their 45 – 55mph margin at 50mph. Going less than 50mph it is more efficient to leave your windows down, but going greater than 50mph it is more efficient to use your A/C.
In comments Lagerbaer suggested that this
Makes sense from a physical point of view: A/C fuel consumption impact should be independent of actual velocity, whereas the drag effect of an open window will grow with the velocity (friction forces in general scale at least linearly with velocity)
While Michael Edenfield suggested the excellent point that
Since the physics concepts involved are the same for all cars, I suspect that more rigorous experiments would produce a different "cut-off point" than 50mph, but the answer to the OP's question is still "AC is better over x mph, worse under x mph". –