diff --git a/changelog.d/2608.change.rst b/changelog.d/2608.change.rst
new file mode 100644
index 0000000000..f966649ae7
--- /dev/null
+++ b/changelog.d/2608.change.rst
@@ -0,0 +1,2 @@
+Added informative error message to PEP 517 build failures owing to
+an empty ``setup.py`` -- by :user:`layday`
diff --git a/setuptools/build_meta.py b/setuptools/build_meta.py
index b9e8a2b3fa..9dfb2f24b5 100644
--- a/setuptools/build_meta.py
+++ b/setuptools/build_meta.py
@@ -101,7 +101,12 @@ def _file_with_extension(directory, extension):
         f for f in os.listdir(directory)
         if f.endswith(extension)
     )
-    file, = matching
+    try:
+        file, = matching
+    except ValueError:
+        raise ValueError(
+            'No distribution was found. Ensure that `setup.py` '
+            'is not empty and that it calls `setup()`.')
     return file
 
 
diff --git a/setuptools/tests/test_build_meta.py b/setuptools/tests/test_build_meta.py
index f33a69688d..ab75a1896c 100644
--- a/setuptools/tests/test_build_meta.py
+++ b/setuptools/tests/test_build_meta.py
@@ -3,6 +3,7 @@
 import tarfile
 import importlib
 from concurrent import futures
+import re
 
 import pytest
 from jaraco import path
@@ -442,6 +443,16 @@ def test_sys_argv_passthrough(self, tmpdir_cwd):
         with pytest.raises(AssertionError):
             build_backend.build_sdist("temp")
 
+    @pytest.mark.parametrize('build_hook', ('build_sdist', 'build_wheel'))
+    def test_build_with_empty_setuppy(self, build_backend, build_hook):
+        files = {'setup.py': ''}
+        path.build(files)
+
+        with pytest.raises(
+                ValueError,
+                match=re.escape('No distribution was found.')):
+            getattr(build_backend, build_hook)("temp")
+
 
 class TestBuildMetaLegacyBackend(TestBuildMetaBackend):
     backend_name = 'setuptools.build_meta:__legacy__'