diff --git a/changelog/762.bugfix.rst b/changelog/762.bugfix.rst
new file mode 100644
index 00000000..83607a41
--- /dev/null
+++ b/changelog/762.bugfix.rst
@@ -0,0 +1,4 @@
+``PluginManager.unregister()`` now raises ``TypeError`` when neither a plugin nor a
+name is given, and ``ValueError`` when an unregistered plugin is given without a
+name, including under ``python -O``. Code catching ``AssertionError`` for these
+cases must catch the new exception types instead.
diff --git a/src/pluggy/_manager.py b/src/pluggy/_manager.py
index 4994c867..2276b15a 100644
--- a/src/pluggy/_manager.py
+++ b/src/pluggy/_manager.py
@@ -283,12 +283,19 @@ def unregister(
         The plugin can be specified either by the plugin object or the plugin
         name. If both are specified, they must agree.
 
-        Returns the unregistered plugin, or ``None`` if not found.
+        Returns the unregistered plugin. When only a name is given, returns
+        ``None`` if the name is not found or is blocked.
+
+        Raises :exc:`TypeError` if neither argument is given, and
+        :exc:`ValueError` if only a plugin object is given but it is not
+        registered, or if the plugin object and name do not agree.
         """
         if name is None:
-            assert plugin is not None, "one of name or plugin needs to be specified"
+            if plugin is None:
+                raise TypeError("one of name or plugin needs to be specified")
             name = self.get_name(plugin)
-            assert name is not None, "plugin is not registered"
+            if name is None:
+                raise ValueError("plugin is not registered")
 
         if plugin is None:
             plugin = self.get_plugin(name)
diff --git a/testing/test_pluginmanager.py b/testing/test_pluginmanager.py
index 4be3dc9a..0d98242b 100644
--- a/testing/test_pluginmanager.py
+++ b/testing/test_pluginmanager.py
@@ -3,6 +3,9 @@
 """
 
 import importlib.metadata
+import subprocess
+import sys
+import textwrap
 import types
 from typing import Any
 from typing import cast
@@ -474,10 +477,58 @@ def he_method1(self): ...  # pragma: no cover
     assert not pm.is_registered(my)
     assert pm.get_plugins() == {my2}
 
-    with pytest.raises(AssertionError, match=r"not registered"):
+    with pytest.raises(ValueError, match=r"not registered"):
         pm.unregister(my)
 
 
+@pytest.mark.parametrize(
+    "kwargs", [{}, {"plugin": None}, {"name": None}, {"plugin": None, "name": None}]
+)
+def test_unregister_requires_argument(
+    pm: PluginManager, kwargs: dict[str, Any]
+) -> None:
+    with pytest.raises(TypeError, match="one of name or plugin needs to be specified"):
+        pm.unregister(**kwargs)
+    assert pm.list_name_plugin() == []
+
+
+@pytest.mark.parametrize("optimization", [0, 1, 2])
+def test_unregister_validation_with_optimization(optimization: int) -> None:
+    result = subprocess.run(
+        [
+            sys.executable,
+            *["-O"] * optimization,
+            "-c",
+            textwrap.dedent(
+                """\
+                from pluggy import PluginManager
+
+                pm = PluginManager("example")
+                for kwargs in ({}, {"plugin": object()}):
+                    try:
+                        pm.unregister(**kwargs)
+                    except (TypeError, ValueError) as exc:
+                        print(f"{type(exc).__name__}: {exc}")
+                """
+            ),
+        ],
+        check=True,
+        capture_output=True,
+        text=True,
+    )
+    assert result.stdout.splitlines() == [
+        "TypeError: one of name or plugin needs to be specified",
+        "ValueError: plugin is not registered",
+    ]
+
+
+def test_unregister_unknown_name(pm: PluginManager) -> None:
+    assert pm.unregister(name="unknown") is None
+    plugin = object()
+    assert pm.unregister(plugin, name="unknown") is plugin
+    assert pm.list_name_plugin() == []
+
+
 def test_unregister_blocked(pm: PluginManager) -> None:
     class Plugin:
         pass
@@ -485,9 +536,11 @@ class Plugin:
     p = Plugin()
     pm.set_blocked("error")
     pm.register(p, "error")
-    # bloked plugins can be unregistred many times atm
-    pm.unregister(p, "error")
-    pm.unregister(p, "error")
+    # Blocked plugins can be unregistered many times.
+    assert pm.unregister(p, "error") is p
+    assert pm.unregister(p, "error") is p
+    assert pm.unregister(name="error") is None
+    assert pm.is_blocked("error")
 
 
 def test_register_unknown_hooks(pm: PluginManager) -> None: