Exhibit 23.1

Consent of Independent Registered Public Accounting Firm

We consent to the incorporation by reference in the following Registration Statements:

1.Registration Statement (Form S-8 No. 333-203755) pertaining to the 2015 Omnibus Incentive Plan,

2.Registration Statement (Form S-8 No. 333-143397) pertaining to the 2007 Outside Director Incentive Plan,

3.Registration Statements (Form S-8 No. 333-191964, No. 333-127341 and No. 333-158903) pertaining to the 2005 Omnibus Incentive Plan,

4.Registration Statements (Form S-8 No. 333-157236, No. 33-37500 and No.333-108321) pertaining to The 401(k) Stock Purchase Plan for Employees of Cullen/Frost Bankers, Inc. and its Affiliates,

5.Registration Statement (Form S-8 No. 33-39478) pertaining to the 1991 Thrift Incentive Stock Purchase Plan for Employees of Cullen/Frost Bankers, Inc. and its Affiliates, and

6.Registration Statement (Form S-3 No. 333-244971) of Cullen/Frost Bankers, Inc.;

of our reports dated February 5, 2021, with respect to the consolidated financial statements of Cullen/Frost Bankers, Inc., and the effectiveness of internal control over financial reporting of Cullen/Frost Bankers, Inc., included in the Annual Report (Form 10-K) for the year ended December 31, 2020.

/s/ Ernst & Young LLP

San Antonio, Texas

February 5, 2021