Microsoft 365 is a subscription that comes with premium apps like Word, Excel, PowerPoint, OneNote, Outlook, Publisher, and Access (Publisher and Access available on PC only). The apps can be installed on multiple devices, including PCs, Macs, iPads, iPhones, Android tablets, and Android phones. Microsoft 365 also comes with services like 1 TB of OneDrive storage, 60 Skype minutes per month, and Microsoft chat and phone support. With a subscription, you get the latest versions of the apps and automatically receive updates when they happen.
Office 2021 is a one-time purchase that comes with classic apps like Word, Excel, and PowerPoint for PC or Mac, and does not include any of the services that come with a Microsoft 365 subscription. One-time purchases don’t have an upgrade option, which means if you plan to upgrade to the next major release, you'll have to buy it at full price.