Yes. Withholding and estimated payments both count toward safe harbor. Estimated payments have to arrive by each quarterly deadline to count in full.
Yes. The safe harbor target is 100% of last year's total tax, or 110% if your prior-year adjusted gross income was over $150,000. You can reach it with withholding, estimated payments, or any mix of the two. What matters is that the money arrived, not how it got there.
The one difference between the two is timing. Withholding counts as paid evenly through the year no matter when it happened. Estimated payments count when they arrive, so the safe harbor protection assumes four equal installments paid by each quarterly deadline. Skipping an early quarter and catching up later still leaves interest owing for the late quarter.
The math is short. Take last year's total tax, apply your 100% or 110%, subtract the withholding you expect this year, and divide what is left by four. That is each installment. Our safe harbor calculator does this in a few seconds.
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Sources: IRS Publication 505· Form 2210 instructions