diff --git a/.changelog/ed6b34a441e64b47affa11a9f5066b23.json b/.changelog/ed6b34a441e64b47affa11a9f5066b23.json
new file mode 100644
index 00000000000..cef5ffde982
--- /dev/null
+++ b/.changelog/ed6b34a441e64b47affa11a9f5066b23.json
@@ -0,0 +1,8 @@
+{
+    "id": "ed6b34a4-41e6-4b47-affa-11a9f5066b23",
+    "type": "bugfix",
+    "description": "aws/signer/v4: Fixes a panic in SDK's handling of endpoint URLs with ports by correcting how URL path is parsed from opaque URLs. Fixes [#1294](https://github.com/aws/aws-sdk-go-v2/issues/1294).",
+    "modules": [
+        "."
+    ]
+}
diff --git a/aws/signer/internal/v4/util.go b/aws/signer/internal/v4/util.go
index 0cb9cffaf51..d025dbaa060 100644
--- a/aws/signer/internal/v4/util.go
+++ b/aws/signer/internal/v4/util.go
@@ -46,19 +46,35 @@ func StripExcessSpaces(str string) string {
 	return string(buf[:m])
 }
 
-// GetURIPath returns the escaped URI component from the provided URL
+// GetURIPath returns the escaped URI component from the provided URL.
 func GetURIPath(u *url.URL) string {
-	var uri string
+	var uriPath string
 
 	if len(u.Opaque) > 0 {
-		uri = "/" + strings.Join(strings.Split(u.Opaque, "/")[3:], "/")
+		const schemeSep, pathSep, queryStart = "//", "/", "?"
+
+		opaque := u.Opaque
+		// Cut off the query string if present.
+		if idx := strings.Index(opaque, queryStart); idx >= 0 {
+			opaque = opaque[:idx]
+		}
+
+		// Cutout the scheme separator if present.
+		if strings.Index(opaque, schemeSep) == 0 {
+			opaque = opaque[len(schemeSep):]
+		}
+
+		// capture URI path starting with first path separator.
+		if idx := strings.Index(opaque, pathSep); idx >= 0 {
+			uriPath = opaque[idx:]
+		}
 	} else {
-		uri = u.EscapedPath()
+		uriPath = u.EscapedPath()
 	}
 
-	if len(uri) == 0 {
-		uri = "/"
+	if len(uriPath) == 0 {
+		uriPath = "/"
 	}
 
-	return uri
+	return uriPath
 }
diff --git a/aws/signer/internal/v4/util_test.go b/aws/signer/internal/v4/util_test.go
index c29c1fa8504..a38ef2d7402 100644
--- a/aws/signer/internal/v4/util_test.go
+++ b/aws/signer/internal/v4/util_test.go
@@ -1,9 +1,92 @@
 package v4
 
 import (
+	"net/http"
+	"net/url"
 	"testing"
 )
 
+func lazyURLParse(v string) func() (*url.URL, error) {
+	return func() (*url.URL, error) {
+		return url.Parse(v)
+	}
+}
+
+func TestGetURIPath(t *testing.T) {
+	cases := map[string]struct {
+		getURL func() (*url.URL, error)
+		expect string
+	}{
+		// Cases
+		"with scheme": {
+			getURL: lazyURLParse("https://localhost:9000"),
+			expect: "/",
+		},
+		"no port, with scheme": {
+			getURL: lazyURLParse("https://localhost"),
+			expect: "/",
+		},
+		"without scheme": {
+			getURL: lazyURLParse("localhost:9000"),
+			expect: "/",
+		},
+		"without scheme, with path": {
+			getURL: lazyURLParse("localhost:9000/abc123"),
+			expect: "/abc123",
+		},
+		"without scheme, with separator": {
+			getURL: lazyURLParse("//localhost:9000"),
+			expect: "/",
+		},
+		"no port, without scheme, with separator": {
+			getURL: lazyURLParse("//localhost"),
+			expect: "/",
+		},
+		"without scheme, with separator, with path": {
+			getURL: lazyURLParse("//localhost:9000/abc123"),
+			expect: "/abc123",
+		},
+		"no port, without scheme, with separator, with path": {
+			getURL: lazyURLParse("//localhost/abc123"),
+			expect: "/abc123",
+		},
+		"opaque with query string": {
+			getURL: lazyURLParse("localhost:9000/abc123?efg=456"),
+			expect: "/abc123",
+		},
+		"failing test": {
+			getURL: func() (*url.URL, error) {
+				endpoint := "https://service.region.amazonaws.com"
+				req, _ := http.NewRequest("POST", endpoint, nil)
+				u := req.URL
+
+				u.Opaque = "//example.org/bucket/key-._~,!@#$%^&*()"
+
+				query := u.Query()
+				query.Set("some-query-key", "value")
+				u.RawQuery = query.Encode()
+
+				return u, nil
+			},
+			expect: "/bucket/key-._~,!@#$%^&*()",
+		},
+	}
+
+	for name, c := range cases {
+		t.Run(name, func(t *testing.T) {
+			u, err := c.getURL()
+			if err != nil {
+				t.Fatalf("failed to get URL, %v", err)
+			}
+
+			actual := GetURIPath(u)
+			if e, a := c.expect, actual; e != a {
+				t.Errorf("expect %v path, got %v", e, a)
+			}
+		})
+	}
+}
+
 func TestStripExcessHeaders(t *testing.T) {
 	vals := []string{
 		"",