diff --git a/icu4c/source/common/uresbund.cpp b/icu4c/source/common/uresbund.cpp
index e95e961a526b..d2746b17d9e0 100644
--- a/icu4c/source/common/uresbund.cpp
+++ b/icu4c/source/common/uresbund.cpp
@@ -1908,6 +1908,8 @@ ures_getByKeyWithFallback(const UResourceBundle *resB,
                             } else {
                               break;
                             }
+                        } else if (res == RES_BOGUS) {
+                            break;
                         }
                     } while(*myPath); /* Continue until the whole path is consumed */
                 }
diff --git a/icu4c/source/test/cintltst/cloctst.c b/icu4c/source/test/cintltst/cloctst.c
index 73124533ee50..b74d5a05c5a9 100644
--- a/icu4c/source/test/cintltst/cloctst.c
+++ b/icu4c/source/test/cintltst/cloctst.c
@@ -280,6 +280,7 @@ void addLocaleTest(TestNode** root)
     TESTCASE(TestBug20370);
     TESTCASE(TestBug20321UnicodeLocaleKey);
     TESTCASE(TestUsingDefaultWarning);
+    TESTCASE(TestBug21449InfiniteLoop);
 }
 
 
@@ -6978,11 +6979,12 @@ static void TestUsingDefaultWarning() {
         log_err("ERROR: in uloc_getDisplayKeywordValue %s %s return len:%d %s with status %d %s\n",
                 keyword_value, keyword, length, errorOutputBuff, status, myErrorName(status));
       }
-}      
+}
+
 // Test case for ICU-20575
 // This test checks if the environment variable LANG is set, 
 // and if so ensures that both C and C.UTF-8 cause ICU's default locale to be en_US_POSIX.
-static void TestCDefaultLocale(){
+static void TestCDefaultLocale() {
     const char *defaultLocale = uloc_getDefault();
     char *env_var = getenv("LANG");
     if (env_var == NULL) {
@@ -6993,3 +6995,13 @@ static void TestCDefaultLocale(){
       log_err("The default locale for LANG=%s should be en_US_POSIX, not %s\n", env_var, defaultLocale);
     }
 }
+
+// Test case for ICU-21449
+static void TestBug21449InfiniteLoop() {
+    UErrorCode status = U_ZERO_ERROR;
+    const char* invalidLocaleId = RES_PATH_SEPARATOR_S;
+
+    // The issue causes an infinite loop to occur when looking up a non-existent resource for the invalid locale ID,
+    // so the test is considered passed if the call to the API below returns anything at all.
+    uloc_getDisplayLanguage(invalidLocaleId, invalidLocaleId, NULL, 0, &status);
+}
diff --git a/icu4c/source/test/cintltst/cloctst.h b/icu4c/source/test/cintltst/cloctst.h
index af7fa5d06a31..69f4e6f1b626 100644
--- a/icu4c/source/test/cintltst/cloctst.h
+++ b/icu4c/source/test/cintltst/cloctst.h
@@ -142,6 +142,7 @@ static void TestToUnicodeLocaleType(void);
 static void TestToLegacyType(void);
 static void TestBug20149(void);
 static void TestCDefaultLocale(void);
+static void TestBug21449InfiniteLoop(void);
 
 
 /**