Any idea why someone would suddenly have their POs require approval? The individual in question is able to create a PO in our Sandbox without incident. No settings have been changed that I can see.

@J-Mack Check their Employee Record and see if a Purchase Limit is assigned. Also I am sure you have already looked but double check and see if the Purchase Order Box is Checked under Setup > Accounting > Accounting Preferences > Approval Routing.

It is unchecked and she has no limit.

Would you happen to be using SuiteApprovals or the Advanced Approvals Suite Solution?

No.