diff --git a/doc/source/whatsnew/v1.1.0.rst b/doc/source/whatsnew/v1.1.0.rst
index e07a8fa0469f4..3304658a37a1a 100644
--- a/doc/source/whatsnew/v1.1.0.rst
+++ b/doc/source/whatsnew/v1.1.0.rst
@@ -167,7 +167,7 @@ MultiIndex
 I/O
 ^^^
 - Bug in :meth:`read_json` where integer overflow was occuring when json contains big number strings. (:issue:`30320`)
--
+- Bug in :meth:`DataFrame.to_json` was raising ``NotFoundError`` when ``path_or_buf`` was an S3 URI (:issue:`28375`)
 -
 
 Plotting
diff --git a/pandas/io/json/_json.py b/pandas/io/json/_json.py
index 204807b55c877..04fd17a00041b 100644
--- a/pandas/io/json/_json.py
+++ b/pandas/io/json/_json.py
@@ -19,12 +19,7 @@
 from pandas.core.construction import create_series_with_explicit_dtype
 from pandas.core.reshape.concat import concat
 
-from pandas.io.common import (
-    get_filepath_or_buffer,
-    get_handle,
-    infer_compression,
-    stringify_path,
-)
+from pandas.io.common import get_filepath_or_buffer, get_handle, infer_compression
 from pandas.io.json._normalize import convert_to_line_delimits
 from pandas.io.json._table_schema import build_table_schema, parse_table_schema
 from pandas.io.parsers import _validate_integer
@@ -56,7 +51,11 @@ def to_json(
             "'index=False' is only valid when 'orient' is 'split' or 'table'"
         )
 
-    path_or_buf = stringify_path(path_or_buf)
+    if path_or_buf is not None:
+        path_or_buf, _, _, _ = get_filepath_or_buffer(
+            path_or_buf, compression=compression, mode="w"
+        )
+
     if lines and orient != "records":
         raise ValueError("'lines' keyword only valid when 'orient' is records")
 
diff --git a/pandas/tests/io/json/test_pandas.py b/pandas/tests/io/json/test_pandas.py
index 94d51589023c4..602022a21c4a6 100644
--- a/pandas/tests/io/json/test_pandas.py
+++ b/pandas/tests/io/json/test_pandas.py
@@ -1662,3 +1662,12 @@ def test_json_multiindex(self, dataframe, expected):
         series = dataframe.stack()
         result = series.to_json(orient="index")
         assert result == expected
+
+    def test_to_s3(self, s3_resource):
+        # GH 28375
+        mock_bucket_name, target_file = "pandas-test", "test.json"
+        df = DataFrame({"x": [1, 2, 3], "y": [2, 4, 6]})
+        df.to_json(f"s3://{mock_bucket_name}/{target_file}")
+        assert target_file in (
+            obj.key for obj in s3_resource.Bucket("pandas-test").objects.all()
+        )