Fetlock joint angle (FJA) pattern is a sensitive indicator of lameness. The first aim of this study is to describe a network of inertial measurement units system (IMUs) for quantifying FJA simultaneously in all limbs. The second aim is to evaluate the accuracy of IMUs for quantifying the sagittal plane FJA overground in comparison to bi-dimensional (2-D) optical motion capture (OMC). 14 horses (7 free from lameness and 7 lame) were enrolled and analyzed with both systems at walk and trot on a firm surface. All enrolled horses were instrumented with 8 IMUs (a pair for each limb) positioned at the dorsal aspect of the metacarpal/metatarsal bone and pastern and acquiring data at 200 Hz. Passive markers were glued on the center of rotation of carpus/tarsus, fetlock, and distal interphalangeal joint, and video footages were captured at 60 Hz and digitalized for OMC acquisition. The IMU system accuracy was reported as Root Mean Square Error (RMSE) and Pearson Correlation Coefficient (PCC). The Granger Causality Test (GCT) and the Bland–Altman analysis were computed between the IMUs and OMC patterns to determine the agreement between the two systems. The proposed IMU system was able to provide FJAs in all limbs using a patented method for sensor calibration and related algorithms. Fetlock joint range of motion (FJROM) variability of three consecutive strides was analyzed in the population through 3-way ANOVA. FJA patterns quantified by IMUs demonstrated high accuracy at the walk (RMSE 8.23° ± 3.74°; PCC 0.95 ± 0.03) and trot (RMSE 9.44° ± 3.96°; PCC 0.96 ± 0.02) on both sound (RMSE 7.91° ± 3.19°; PCC 0.97 ± 0.03) and lame horses (RMSE 9.78° ± 4.33°; PCC 0.95 ± 0.03). The two systems’ measurements agreed (mean bias around 0) and produced patterns that were in temporal agreement in 97.33% of the cases (p < 0.01). The main source of variability between left and right FJROM in the population was the presence of lameness (p < 0.0001) and accounted for 28.46% of this total variation. IMUs system accurately quantified sagittal plane FJA at walk and trot in both sound and lame horses.