This paper studies commutativity of sixth-order differential systems with zero and nonzero initial conditions (ICs). Given a sixth-order differential system A, we find its commutative pair, that is a new differential system B of order m <= 6; the obtained result will be used to show the input-output equivalency between the cascaded-connected systems AB and BA. Necessary and sufficient conditions for commutativity of sixth-order continuous-time linear time-varying systems (CTLTVSs) are derived. Based on our findings, we discovered that only a small group of sixth-order CTLTVSs has commutative pairs other than their feedback conjugates obtained by constant feedback and forward path gains. The explicit results obtained in this paper will help to fill the gap on commutativity theory, system behaviors which has significant application to science and play an important role in engineering. This research will also address the problems of sensitivity due to changes in ICs or parameters, and also disturbance as a result of external noise. The results are well verified by examples as well as validated by Matlab Simulink tool and Wolfram Mathematica 11.