The aim of the current study was to propose a generalized magic angle effect (gMAE) function for characterizing anisotropic T2W signals of human knee femoral cartilage with a spherical surface in clinical studies. A gMAE model function f(α, ε) was formulated for an orientation-dependent (ε) transverse T 2 (i.e., 1/R 2 ) relaxation in cartilage assuming an axially symmetric distribution (α) of collagen fibers. T2W sagittal images were acquired on an adult volunteer's healthy knee at 3 T, and ROI-based average signals S(ε) were extracted from angularly and radially segmented femoral cartilage.Compared with the standard MAE (sMAE) functions in the deep (DZ, α = 0 ) and in the superficial (SZ, α = 90 ) zones, a general form of R 2 orientation-dependent function f(α, ε) was fitted to S(ε), including an isotropic R 2 contribution (internal reference [REF]). Goodness of fit was evaluated by root-mean-square deviations (RMSDs).An F-test and a paired t-test were respectively used to assess significant differences between the observed variances and means, with statistical significance set to p less than .05. As a symmetric orientation-dependence function with a varying dynamic range, the proposed gMAE model outperformed the previous sMAE functions manifested by significantly reduced RMSDs in the DZ (0.239 ± 0.122 vs. 0.267 ± 0.097, p = .014) and in the SZ (0.183 ± 0.081 vs. 0.254 ± 0.085, p < .001). The fitted average angle α (38.5 ± 34.6 vs. 45.1 ± 30.1 , p < .43) and REF (5.092 ± 0.369 vs. 5.305 ± 0.440, p < .001) were smaller in the DZ than those in SZ, in good agreement with the reported collagen fibril microstructural configurations and the nonbound water contribution to R 2 in articular cartilage. In conclusion, a general form of the magic angle effect function was proposed and demonstrated for better characterizing anisotropic T2W signals from human knee femoral cartilage at 3 T in clinical studies.