diff --git a/.changes/next-release/bugfix-generatepresignedurl-96454.json b/.changes/next-release/bugfix-generatepresignedurl-96454.json
new file mode 100644
index 0000000000..1f1bed810e
--- /dev/null
+++ b/.changes/next-release/bugfix-generatepresignedurl-96454.json
@@ -0,0 +1,5 @@
+{
+  "type": "bugfix",
+  "category": "``Polly``",
+  "description": "Remove `Content-Type` header from ``synthesize_speech`` URL presigning."
+}
diff --git a/botocore/handlers.py b/botocore/handlers.py
index 3014123f9b..9546c61128 100644
--- a/botocore/handlers.py
+++ b/botocore/handlers.py
@@ -1137,6 +1137,14 @@ def customize_endpoint_resolver_builtins(
         builtins[EndpointResolverBuiltins.AWS_S3_USE_GLOBAL_ENDPOINT] = True
 
 
+def remove_content_type_header_for_presigning(request, **kwargs):
+    if (
+        request.context.get('is_presign_request') is True
+        and 'Content-Type' in request.headers
+    ):
+        del request.headers['Content-Type']
+
+
 # This is a list of (event_name, handler).
 # When a Session is created, everything in this list will be
 # automatically registered with that Session.
@@ -1240,6 +1248,10 @@ def customize_endpoint_resolver_builtins(
     ('before-parameter-build.route53', fix_route53_ids),
     ('before-parameter-build.glacier', inject_account_id),
     ('before-sign.s3', remove_arn_from_signing_path),
+    (
+        'before-sign.polly.SynthesizeSpeech',
+        remove_content_type_header_for_presigning,
+    ),
     ('after-call.s3.ListObjects', decode_list_object),
     ('after-call.s3.ListObjectsV2', decode_list_object_v2),
     ('after-call.s3.ListObjectVersions', decode_list_object_versions),
diff --git a/tests/unit/test_signers.py b/tests/unit/test_signers.py
index 5b05c7fea8..92a3d5da3f 100644
--- a/tests/unit/test_signers.py
+++ b/tests/unit/test_signers.py
@@ -13,6 +13,7 @@
 import datetime
 import json
 
+import pytest
 from dateutil.tz import tzutc
 
 import botocore
@@ -39,6 +40,13 @@
 from tests import assert_url_equal, mock, unittest
 
 
+@pytest.fixture
+def polly_client():
+    session = botocore.session.get_session()
+    session.set_credentials('key', 'secret')
+    return session.create_client('polly', region_name='us-west-2')
+
+
 class BaseSignerTest(unittest.TestCase):
     def setUp(self):
         self.credentials = Credentials('key', 'secret')
@@ -1168,3 +1176,23 @@ def test_custom_region(self):
         self.assertIn(region, result)
         # The hostname won't be changed even if a different region is specified
         self.assertIn(hostname, result)
+
+
+@pytest.mark.parametrize(
+    'request_method',
+    ['GET', 'HEAD', 'OPTIONS', 'POST', 'PUT', 'DELETE', None],
+)
+def test_generate_presigned_url_content_type_removal_for_polly(
+    polly_client,
+    request_method,
+):
+    url = polly_client.generate_presigned_url(
+        'synthesize_speech',
+        Params={
+            'OutputFormat': 'mp3',
+            'Text': 'Hello world!',
+            'VoiceId': 'Joanna',
+        },
+        HttpMethod=request_method,
+    )
+    assert 'content-type' not in url.lower()