Background: COVID-19 is an ongoing global pandemic caused by SARS-CoV-2. As of June 2021, 5 emergency vaccines were available for COVID-19 prevention, and with the improvement of vaccination rates and the resumption of activities in each country, verification of vaccination has become an important issue. Currently, in most areas, vaccination and reverse transcription polymerase chain reaction (RT-PCR) test results are certified and validated on paper. This leads to the problem of counterfeit documents. Therefore, a global vaccination record is needed. Objective: The main objective of this study is to design a vaccine passport (VP) validation system based on a general blockchain architecture for international use in a simulated environment. With decentralized characteristics, the system is expected to have the advantages of low cost, high interoperability, effectiveness, security, and verifiability through blockchain architecture. Methods: The blockchain decentralized mechanism was used to build an open and anticounterfeiting information platform for VPs. The contents of a vaccination card are recorded according to international Fast Healthcare Interoperability Resource (FHIR) standards, and blockchain smart contracts (SCs) are used for authorization and authentication to achieve hierarchical management of various international hospitals and people receiving injections. The blockchain stores an encrypted vaccination path managed by the user who manages the private key. The blockchain uses the proof-of-authority (PoA) public chain and can access all information through the specified chain. This will achieve the goal of keeping development costs low and streamlining vaccine transit management so that countries in different economies can use them. Results: The openness of the blockchain helps to create transparency and data accuracy. This blockchain architecture contains a total of 3 entities. All approvals are published on Open Ledger. Smart certificates enable authorization and authentication, and encryption and decryption mechanisms guarantee data protection. This proof of concept demonstrates the design of blockchain architecture, which can achieve accurate global VP verification at an affordable price. In this study, an actual VP case was established and demonstrated. An open blockchain, an individually approved certification mechanism, and an international standard vaccination record were introduced. Conclusions: Blockchain architecture can be used to build a viable international VP authentication process with the advantages of low cost, high interoperability, effectiveness, security, and verifiability.