diff --git a/news/4608.rst b/news/4608.rst
new file mode 100644
index 0000000000..94395bff99
--- /dev/null
+++ b/news/4608.rst
@@ -0,0 +1,23 @@
+**Added:**
+
+* <news item>
+
+**Changed:**
+
+* #4608 Expand `'~'` in $VIRTUALENV_HOME when used by vox
+
+**Deprecated:**
+
+* <news item>
+
+**Removed:**
+
+* <news item>
+
+**Fixed:**
+
+* <news item>
+
+**Security:**
+
+* <news item>
diff --git a/tests/test_vox.py b/tests/test_vox.py
index cf9942bf17..ee4f6998d4 100644
--- a/tests/test_vox.py
+++ b/tests/test_vox.py
@@ -7,6 +7,7 @@
 import sys
 import types
 from typing import TYPE_CHECKING
+from unittest.mock import ANY, MagicMock
 
 import pytest
 from py.path import local
@@ -170,6 +171,31 @@ def test_vox_flow(xession, vox, record_events, venv_home):
     assert record_events.last == ("vox_on_delete", "spam")
 
 
+@pytest.mark.parametrize(
+    "env_venv_home",
+    [
+        pathlib.Path("~", ".custom_home_dir/"),
+        pathlib.Path("~root", "venv"),
+        pathlib.Path(".rel_venv"),
+        pathlib.Path("/tmp", "abs_venv"),
+        None,
+    ],
+)
+def test_venvdir_expand(xession, env_venv_home):
+    venv_name = "test_xonsh_venv"
+
+    if env_venv_home:
+        xession.env["VIRTUALENV_HOME"] = str(env_venv_home)
+        expected_dir = str((env_venv_home / venv_name).expanduser())
+    else:
+        expected_dir = str(pathlib.Path("~", ".virtualenvs", venv_name).expanduser())
+    vox = Vox()
+    vox._create = MagicMock()
+    vox.create(venv_name)
+
+    vox._create.assert_called_with(expected_dir, ANY, False, False, True, prompt=None)
+
+
 def test_activate_non_vox_venv(xession, vox, record_events, venv_proc, venv_home):
     """
     Create a virtual environment using Python's built-in venv module
diff --git a/xontrib/voxapi.py b/xontrib/voxapi.py
index 01c79bacd4..78237bd616 100644
--- a/xontrib/voxapi.py
+++ b/xontrib/voxapi.py
@@ -22,6 +22,7 @@
 # FIXME: Is there a better way?
 from xonsh.events import events
 from xonsh.platform import ON_POSIX, ON_WINDOWS
+from xonsh.tools import expand_path
 
 events.doc(
     "vox_on_create",
@@ -128,7 +129,7 @@ def __init__(self, force_removals=False):
             self.venvdir = os.path.join(home_path, ".virtualenvs")
             XSH.env["VIRTUALENV_HOME"] = self.venvdir
         else:
-            self.venvdir = XSH.env["VIRTUALENV_HOME"]
+            self.venvdir = expand_path(XSH.env["VIRTUALENV_HOME"])
         self.force_removals = force_removals
         self.sub_dirs = _subdir_names()