Polyurethane (PU) has been used in clinical practice for artificial meniscus to alleviate the distress of patients with meniscus injury, but the high friction of PU in synovial fluid can lead to the deterioration of knee joints. In this work, PUs with sulfobetaine zwitterions modified by hydrophobic chains in bulk (PU-hSBs) are synthesized to solve the above-mentioned challenge, and the lubrication behavior and mechanism of PU-hSBs in the aqueous solution of representative synovial components that mimic the in vivo environment of synovial fluid to some extent are studied. Among the above materials, PU-hSB70 can meet the low friction of an artificial meniscus and also has appropriate tensile modulus and low cytotoxicity. Moreover, PU-hSB70 can maintain excellent tribological and mechanical properties after prolonged immersion and compressive fatigue tests, which support its long-term application in vivo. Additionally, the lubrication role of synovial components is identified by contrasting the lubrication behavior of PU-hSBs in deionized water after excluding the effect of the lubricant viscosity. A formed hydration layer of noncrystal water is improved by the hydration of the complexes of phosphatidylcholine-hyaluronic acid adsorbed onto PU-hSB70 via hydrophobic and electrostatic interactions. However, the presence of serum protein on PU-hSB70, which interacts hydrophobically, has a diminishing effect on the thickness of the layer. Our results show the potential of PU-hSB70 can be used as an artificial meniscus. Furthermore, the lubrication chemistry and mechanism of representative synovial components are deeply proven through hydration.