Background and Objective Inebilizumab is a humanized, affinity-optimized, afucosylated immunoglobulin (Ig)-G1κ monoclonal antibody that binds to CD19, resulting in effective depletion of peripheral B cells. It is being developed to treat various autoimmune diseases, including neuromyelitis optica spectrum disorders (NMOSD), systemic sclerosis (SSc), and relapsing multiple sclerosis (MS). Methods Pharmacokinetic data from a pivotal study in adult subjects with NMOSD and two early-stage studies in subjects with SSc or relapsing MS were pooled and simultaneously analyzed using a population approach. Results Upon intravenous administration, the pharmacokinetics of inebilizumab were adequately described by a two-compartment model with parallel first-order and time-dependent nonlinear elimination pathways. An asymptotic nonlinear elimination suggests that inebilizumab undergoes receptor (CD19)-mediated clearance. The estimated systemic clearance (CL) of the first-order elimination pathway (0.188 L/day) and the volume of distribution ( V d ) (5.52 L) were typical for therapeutic immunoglobulins. The elimination half-life was approximately 18 days. The maximum velocity ( V max ) of the nonlinear elimination pathway decreased with time, presumably due to the depletion of B cells upon inebilizumab administration. As for other therapeutic monoclonal antibodies, the CL and V d of inebilizumab increased with body weight. Conclusions The presence of antidrug antibodies, status of hepatic or renal function, and use of small-molecule drugs commonly used by subjects with NMOSD had no clinically relevant impact on the pharmacokinetics of inebilizumab. The nonlinear elimination pathway at the 300 mg therapeutic dose level is not considered clinically relevant.