This paper proposes a parameter identification method for fractional-order time-delay systems with measurement noise, based on the Legendre wavelet variable-period integration operational matrix. A variable-period integration operational matrix and a variable-period time-delay integration operational matrix are constructed by variable-period sampling principle. For the impulse noise, global Gaussian noise and local Gaussian noise present in the identification data, the variable-period sampling, operational matrix global coefficient decomposition and matrix local coefficient decomposition methods are used to reconstruct the variable-period integration operational matrix to separate the noise from the data; the fractional-order time-delay system is expressed as an integral equation by using the reconstructed variable-period operational matrix, this reduces the influence of measurement noise on system identification accuracy. To further improve the parameter identification accuracy, the integral equation is solved by the multi-innovation least squares algorithm. The proposed method’s effectiveness is verified through several simulations and an experimental study of a constant-temperature system.