For a new US store, tax setup has three steps: figure out where you have nexus, turn on Shopify's automatic tax calculation for those places, and register for the sales tax permits you actually need. Most new merchants either ignore taxes entirely or drown in research. Aim for the middle: correct in the states where you clearly owe, and revisit as you grow.
Nexus is the legal connection that obligates you to collect sales tax in a state. For a new store, nexus almost always starts with your home state: if you live there, run the business from there, or hold inventory there, you have nexus there. Beyond that, most states have economic nexus thresholds, commonly $100,000 in sales or 200 transactions into the state per year, though the exact numbers vary. A brand-new store rarely crosses those on day one, so your list is usually short: your home state, plus anywhere you store inventory or have employees.
In the Shopify admin, under Settings then Taxes and duties, you set the regions where you collect. Shopify Tax, included on current plans for US stores, calculates the correct rate automatically, including the county and city layers that make manual tables hopeless. Add each region where you have nexus, confirm the product tax categories look right for what you sell, and let the system do the math. The default categories are correct for ordinary physical products; digital goods and some categories like clothing have state-specific quirks worth a glance.
Collecting tax without a permit is the mistake to avoid. Most states require you to register for a sales tax permit before you collect a dollar, and the registration is usually free or cheap through the state's revenue department website. Do this for each state where you have nexus before you start collecting there. The permit also sets your filing schedule: monthly, quarterly, or annually, based on your volume. Put the filing deadlines on a calendar the day you register, because the penalties for missing a filing are what actually sting.
Collecting tax in states where you have no obligation creates registration and filing work for no reason, and some states make it hard to stop once you start. A new store selling nationwide does not collect in all fifty states. It collects in the handful where it has nexus, and Shopify only charges tax at checkout for the regions you configured. As sales grow, check your numbers against each state's economic threshold once a quarter and add registrations when you cross them.
Most physical products are taxed straightforwardly, but a few categories have quirks. Clothing is exempt or partially exempt in several states. Digital products and gift cards have their own rules. Shipping charges are taxable in some states and not in others. If your catalog is mostly standard physical goods, the defaults will carry you. If you sell in an exception category, spend the extra hour on that state's rules before launch rather than discovering the problem in an audit.
Tax setup is not a launch-week fire to fight daily. Get the home state right, register, turn on automatic calculation, and put a quarterly review on the calendar: check sales by state against nexus thresholds, confirm filings are done, and adjust the region list. That rhythm keeps a growing store compliant without turning taxes into a second job.