If my spouse has a W-2 job, can extra withholding cover my self-employment taxes?

Yes, and it is one of the cleanest ways to handle SE taxes on a married joint return. Withholding from a W-2 paycheck is treated by the IRS as paid evenly throughout the year, regardless of when it actually came out. So your spouse can bump up withholding on their W-4 to cover your business tax, and it retroactively satisfies the pay-as-you-go rule for all four quarters. That can eliminate the need for you to send separate quarterly estimates entirely, and it sidesteps underpayment penalties even if you increase withholding late in the year. Coordinate the numbers so you still hit a safe harbor: 90% of this year's tax or 100% to 110% of last year's.