My wife will work 2 more years at $100,000 a year. Our monthly payment is $975 with a $125,000 balance. We have a combined 401K with $380,000. Should we pay off our mortgage by withdrawing from our 401KI ?

Not enough info. Interest rate on loan, her SS amount, other savings, what you plan to do in retirement, how healthy you are, will you downsize, etc.
I would sit down with a financial planner or book or online calculator in 2 years.

NEVER withdraw from a 401(k) to pay off a mortgage. Find a well-respected CPA/financial planner. You might check into a reverse mortgage if you plan to stay in your house for the rest of your lives.

I agree that it is not a good idea to use a tax-advantaged account to pay down your mortgage. One thing to consider is refinancing your mortgage - what is the interest rate on it? Paying $975/month on a $125K mortgage balance seems high, unless you have only a few more years on the mortgage and most your payment is going toward principal. If you refinance the balance on a new 30-year mortgage your monthly payment would be reduced to about $685.