A cardiac rhythm management system including a highly sensitive technique for discriminating AF from AFL. An electrode disposed in or about a heart senses a cardiac signal. A controller through a sensing circuit receives the sensed cardiac signal from the electrode and processes the sensed cardiac signal to compute an average cycle length-to-cycle length variation based on serial interval relationships from the sensed cardiac signal, and then comparing the computed average cycle length-to-cycle length variation to one or more pre-determined threshold values to discriminate AF from AFL. As a result of substantial difference in cycle length-to-cycle length variation between AF and AFL (despite similar average cycle lengths), the sequence-based measure of cycle length-to-cycle length variability proves to be a highly specific and reliable discriminator of AF from AFL.