Lenvatinib (Lenvima) is a tyrosine kinase inhibitor on the market and has been used for the treatment of various types of cancer. It is important to understand differences in pharmacokinetics (PK) between nonclinical animals and humans, and thus, we evaluated PK of lenvatinib in mice, rats, dogs, and monkeys. A simple assay for lenvatinib was developed by high performance liquid chromatography with ultraviolet detection and validated in accordance with the bioanalytical guidelines. Lenvatinib was quantifiable at 5–100,000 ng/mL using 50 μL of plasma. Accuracy and precision in the intra- and inter-batch reproducibility were within the acceptance criteria, indicating a robust assay. Lenvatinib was intravenously or orally administered to mice, rats, dogs, and monkeys to fully characterize the cross-species PK. Total clearance and volume of distribution were relatively low and bioavailability of lenvatinib was approximately 64–78% in all the species tested. PK of lenvatinib in mice and rats after oral dose was almost linear at the doses ranging from 3 to 30 mg/kg. An empirical allometric scaling successfully predicted oral systemic exposure of lenvatinib in humans. Collectively, PK profiles of lenvatinib in nonclinical animals were well characterized and were useful for PK prediction in humans.