diff --git a/doc/source/cookbook/fits_radio_cubes.ipynb b/doc/source/cookbook/fits_radio_cubes.ipynb
index c34eafbb0f9..889ee3aacaa 100644
--- a/doc/source/cookbook/fits_radio_cubes.ipynb
+++ b/doc/source/cookbook/fits_radio_cubes.ipynb
@@ -18,7 +18,7 @@
    "source": [
     "This notebook demonstrates some of the capabilities of yt on some FITS \"position-position-spectrum\" cubes of radio data.\n",
     "\n",
-    "Note that it depends on some external dependencies, including `astropy` and `pyregion`."
+    "Note that it depends on some external dependencies, including `astropy` and `regions`."
    ]
   },
   {
@@ -413,7 +413,7 @@
    "cell_type": "markdown",
    "metadata": {},
    "source": [
-    "Finally, we can also take an existing [ds9](http://ds9.si.edu/site/Home.html) region and use it to create a \"cut region\" as well, using `ds9_region` (the [pyregion](https://pyregion.readthedocs.io/) package needs to be installed for this):"
+    "Finally, we can also take an existing [ds9](http://ds9.si.edu/site/Home.html) region and use it to create a \"cut region\" as well, using `ds9_region` (the [regions](https://astropy-regions.readthedocs.io/) package needs to be installed for this):"
    ]
   },
   {
diff --git a/doc/source/cookbook/fits_xray_images.ipynb b/doc/source/cookbook/fits_xray_images.ipynb
index d0b73f201a8..9124658317d 100644
--- a/doc/source/cookbook/fits_xray_images.ipynb
+++ b/doc/source/cookbook/fits_xray_images.ipynb
@@ -258,7 +258,7 @@
    "cell_type": "markdown",
    "metadata": {},
    "source": [
-    "Finally, we can also take an existing [ds9](http://ds9.si.edu/site/Home.html) region and use it to create a \"cut region\", using `ds9_region` (the [pyregion](https://pyregion.readthedocs.io) package needs to be installed for this):"
+    "Finally, we can also take an existing [ds9](http://ds9.si.edu/site/Home.html) region and use it to create a \"cut region\", using `ds9_region` (the [regions](https://astropy-regions.readthedocs.io/) package needs to be installed for this):"
    ]
   },
   {
diff --git a/doc/source/examining/loading_data.rst b/doc/source/examining/loading_data.rst
index bcda9eb14de..a06a1c97c67 100644
--- a/doc/source/examining/loading_data.rst
+++ b/doc/source/examining/loading_data.rst
@@ -1232,7 +1232,7 @@ and add them to the field registry for the dataset ``ds``.
 This function takes a `ds9 <http://ds9.si.edu/site/Home.html>`_ region and
 creates a "cut region" data container from it, that can be used to select
 the cells in the FITS dataset that fall within the region. To use this
-functionality, the `pyregion <https://github.com/astropy/pyregion/>`_
+functionality, the `regions <https://github.com/astropy/regions/>`_
 package must be installed.
 
 .. code-block:: python
diff --git a/setup.cfg b/setup.cfg
index 7c4b5f4d36e..af6f7ab2b35 100644
--- a/setup.cfg
+++ b/setup.cfg
@@ -66,8 +66,8 @@ doc =
     jinja2<3.1.0  # see https://github.com/readthedocs/readthedocs.org/issues/9037
     jupyter-client<7.0
     nbconvert==5.6.1
-    pyregion
     pyx>=0.15
+    regions>=0.7
     runnotebook
     scipy<=1.7.1  # see https://github.com/yt-project/yt/issues/3966 and https://github.com/scipy/scipy/issues/16602
     sphinx==3.1.2
diff --git a/yt/frontends/fits/misc.py b/yt/frontends/fits/misc.py
index 29d5381de2c..7a105d5cc2d 100644
--- a/yt/frontends/fits/misc.py
+++ b/yt/frontends/fits/misc.py
@@ -135,8 +135,8 @@ def create_spectral_slabs(filename, slab_centers, slab_width, **kwargs):
 
 def ds9_region(ds, reg, obj=None, field_parameters=None):
     r"""
-    Create a data container from a ds9 region file. Requires the pyregion
-    package (https://pyregion.readthedocs.io/en/latest/) to be installed.
+    Create a data container from a ds9 region file. Requires the regions
+    package (https://astropy-regions.readthedocs.io/) to be installed.
 
     Parameters
     ----------
@@ -157,21 +157,29 @@ def ds9_region(ds, reg, obj=None, field_parameters=None):
     >>> circle_region = ds9_region(ds, "circle.reg")
     >>> print(circle_region.quantities.extrema("flux"))
     """
-    import pyregion
+    from regions import Regions
+
+    from yt.utilities.on_demand_imports import _astropy
+
+    WCS = _astropy.WCS
 
     from yt.frontends.fits.api import EventsFITSDataset
 
     if os.path.exists(reg):
-        r = pyregion.open(reg)
+        method = Regions.read
     else:
-        r = pyregion.parse(reg)
+        method = Regions.parse
+    r = method(reg, format="ds9").regions[0]
+
     reg_name = reg
     header = ds.wcs_2d.to_header()
     # The FITS header only contains WCS-related keywords
-    header["NAXIS1"] = nx = ds.domain_dimensions[ds.lon_axis]
-    header["NAXIS2"] = ny = ds.domain_dimensions[ds.lat_axis]
-    filter = r.get_filter(header=header)
-    mask = filter.mask((ny, nx)).transpose()
+    header["NAXIS1"] = ds.domain_dimensions[ds.lon_axis]
+    header["NAXIS2"] = ds.domain_dimensions[ds.lat_axis]
+
+    pixreg = r.to_pixel(WCS(header))
+    mask = pixreg.to_mask().data.astype(bool)
+
     if isinstance(ds, EventsFITSDataset):
         prefix = "event_"
     else:
diff --git a/yt/utilities/on_demand_imports.py b/yt/utilities/on_demand_imports.py
index 6f593b59b40..cdda96537cb 100644
--- a/yt/utilities/on_demand_imports.py
+++ b/yt/utilities/on_demand_imports.py
@@ -135,6 +135,13 @@ def wcsaxes(self):
         self.log
         return wcsaxes
 
+    @safe_import
+    def WCS(self):
+        from astropy.wcs import WCS
+
+        self.log
+        return WCS
+
 
 _astropy = astropy_imports()