diff --git a/docs/data-model.rst b/docs/data-model.rst
index a589006bd3..159fc8124e 100644
--- a/docs/data-model.rst
+++ b/docs/data-model.rst
@@ -501,6 +501,8 @@ interchanged, each row is `base 64 encoded <https://en.wikipedia.org/wiki/Base64
 Thus, binary information can be safely printed and exchanged, but may not be
 human readable.
 
+The tree sequence itself also has metadata stored as a byte array.
+
 .. _sec_valid_tree_sequence_requirements:
 
 Valid tree sequence requirements
diff --git a/docs/metadata.rst b/docs/metadata.rst
index ad40d59efd..cadd960858 100644
--- a/docs/metadata.rst
+++ b/docs/metadata.rst
@@ -4,7 +4,7 @@
 Metadata
 ========
 
-Every entity (nodes, mutations, edges,  etc.) in a tskit tree sequence can have
+The tree-sequence and every entity within it (nodes, mutations, edges,  etc.) can have
 metadata associated with it. This is intended for storing and passing on information
 that tskit itself does not use or interpret. For example information derived from a VCF
 INFO field, or administrative information (such as unique identifiers) relating to
@@ -170,11 +170,17 @@ attribute (e.g. :attr:`tskit.IndividualTable.metadata_schema`). The schemas
 for all tables can be retrieved from a :class:`tskit.TreeSequence` by the
 :attr:`tskit.TreeSequence.table_metadata_schemas` attribute.
 
+The top-level tree sequence metadata schema is set via
+:attr:`tskit.TableCollection.metadata_schema` and can be accessed via
+:attr:`tskit.TreeSequence.metadata_schema`.
+
 Each table's ``add_row`` method (e.g. :meth:`tskit.IndividualTable.add_row`) will
-validate and encode the metadata using the schema.
+validate and encode the metadata using the schema. This encoding will also happen when
+tree sequence metadata is set (e.g. ``table_collection.metadata = {...}``.
 
 Metadata will be lazily decoded if accessed via
-``tables.individuals[0].metadata`` or ``tree_sequence.individual(0).metadata``.
+``tables.individuals[0].metadata``.  ``tree_sequence.individual(0).metadata`` or
+``tree_sequence.metadata``
 
 In the interests of efficiency the bulk methods of ``set_columns``
 (e.g. :meth:`tskit.IndividualTable.set_columns`)
diff --git a/python/CHANGELOG.rst b/python/CHANGELOG.rst
index 1c65d6c03a..8611ce6d8b 100644
--- a/python/CHANGELOG.rst
+++ b/python/CHANGELOG.rst
@@ -27,6 +27,9 @@ In development
   on calls to ``table[j]`` and e.g. ``tree_sequence.node(j)`` See :ref:`sec_metadata`.
   (:user:`benjeffery`, :pr:`491`, :pr:`542`, :pr:`543`, :pr:`601`)
 
+- The tree-sequence now has top-level metadata with a schema.
+  (:user:`benjeffery`, :pr:`666`, :pr:`644`, :pr:`642`)
+
 - Add classes to SVG drawings to allow easy adjustment and styling, and document the new
   ``tskit.Tree.draw_svg()`` and ``tskit.TreeSequence.draw_svg()`` methods. This also fixes
   :issue:`467` for duplicate SVG entity ``id`` s in Jupyter notebooks.
diff --git a/python/tests/test_highlevel.py b/python/tests/test_highlevel.py
index 1014aa90ad..9f0d1059df 100644
--- a/python/tests/test_highlevel.py
+++ b/python/tests/test_highlevel.py
@@ -1368,7 +1368,37 @@ class TestTreeSequenceMetadata(unittest.TestCase):
         },
     )
 
-    def test_metadata_schemas(self):
+    def test_tree_sequence_metadata_schema(self):
+        tc = tskit.TableCollection(1)
+        ts = tc.tree_sequence()
+        self.assertEqual(str(ts.metadata_schema), str(tskit.MetadataSchema(None)))
+        tc.metadata_schema = self.metadata_schema
+        ts = tc.tree_sequence()
+        self.assertEqual(str(ts.metadata_schema), str(self.metadata_schema))
+        with self.assertRaises(AttributeError):
+            del ts.metadata_schema
+        with self.assertRaises(AttributeError):
+            ts.metadata_schema = tskit.MetadataSchema(None)
+
+    def test_tree_sequence_metadata(self):
+        tc = tskit.TableCollection(1)
+        ts = tc.tree_sequence()
+        self.assertEqual(ts.metadata, b"")
+        tc.metadata_schema = self.metadata_schema
+        data = {
+            "table": "tree-sequence",
+            "string_prop": "stringy",
+            "num_prop": 42,
+        }
+        tc.metadata = data
+        ts = tc.tree_sequence()
+        self.assertEqual(ts.metadata, data)
+        with self.assertRaises(AttributeError):
+            ts.metadata = {"should": "fail"}
+        with self.assertRaises(AttributeError):
+            del ts.metadata
+
+    def test_table_metadata_schemas(self):
         ts = msprime.simulate(5)
         for table in self.metadata_tables:
             tables = ts.dump_tables()
@@ -1405,7 +1435,7 @@ def test_metadata_schemas(self):
                         tskit.MetadataSchema({"codec": "json"}),
                     )
 
-    def test_metadata_round_trip_via_row_getters(self):
+    def test_table_metadata_round_trip_via_row_getters(self):
         # A tree sequence with all entities
         pop_configs = [msprime.PopulationConfiguration(5) for _ in range(2)]
         migration_matrix = [[0, 1], [1, 0]]
diff --git a/python/tests/test_tables.py b/python/tests/test_tables.py
index 062c972c6d..a4f7e3e75f 100644
--- a/python/tests/test_tables.py
+++ b/python/tests/test_tables.py
@@ -2109,6 +2109,103 @@ def test_sequence_length_longer_than_edges(self):
         self.assertEqual(len(tree.parent_dict), 0)
 
 
+class TestTableCollectionMetadata(unittest.TestCase):
+
+    metadata_schema = metadata.MetadataSchema(
+        {
+            "codec": "json",
+            "title": "Example Metadata",
+            "type": "object",
+            "properties": {
+                "one": {"type": "string"},
+                "two": {"type": "number"},
+                "three": {"type": "array"},
+                "four": {"type": "boolean"},
+            },
+            "required": ["one", "two", "three", "four"],
+            "additionalProperties": False,
+        },
+    )
+
+    def metadata_example_data(self, val=0):
+        return {
+            "one": "val one",
+            "two": val,
+            "three": list(range(val, val + 10)),
+            "four": True,
+        }
+
+    def test_set_metadata_schema(self):
+        tc = tskit.TableCollection(1)
+        metadata_schema2 = metadata.MetadataSchema({"codec": "json"})
+        # Default is no-op metadata codec
+        self.assertEqual(str(tc.metadata_schema), str(metadata.MetadataSchema(None)))
+        # Set
+        tc.metadata_schema = self.metadata_schema
+        self.assertEqual(str(tc.metadata_schema), str(self.metadata_schema))
+        # Overwrite
+        tc.metadata_schema = metadata_schema2
+        self.assertEqual(str(tc.metadata_schema), str(metadata_schema2))
+        # Remove
+        tc.metadata_schema = ""
+        self.assertEqual(str(tc.metadata_schema), str(metadata.MetadataSchema(None)))
+        # Set after remove
+        tc.metadata_schema = self.metadata_schema
+        self.assertEqual(str(tc.metadata_schema), str(self.metadata_schema))
+        # Del should fail
+        with self.assertRaises(AttributeError):
+            del tc.metadata_schema
+        # None should fail
+        with self.assertRaises(ValueError):
+            tc.metadata_schema = None
+
+    def test_set_metadata(self):
+        tc = tskit.TableCollection(1)
+        # Default is empty bytes
+        self.assertEqual(tc.metadata, b"")
+
+        tc.metadata_schema = self.metadata_schema
+        md1 = self.metadata_example_data()
+        md2 = self.metadata_example_data(val=2)
+        # Set
+        tc.metadata = md1
+        self.assertEqual(tc.metadata, md1)
+        # Overwrite
+        tc.metadata = md2
+        self.assertEqual(tc.metadata, md2)
+        # Del should fail
+        with self.assertRaises(AttributeError):
+            del tc.metadata
+        # None should fail
+        with self.assertRaises(exceptions.MetadataValidationError):
+            tc.metadata = None
+
+    def test_default_metadata_schema(self):
+        # Default should allow bytes
+        tc = tskit.TableCollection(1)
+        tc.metadata = b"acceptable bytes"
+        self.assertEqual(tc.metadata, b"acceptable bytes")
+        # Adding non-bytes metadata should error
+        with self.assertRaises(TypeError):
+            tc.metadata = self.metadata_example_data()
+
+    def test_round_trip_metadata(self):
+        data = self.metadata_example_data()
+        tc = tskit.TableCollection(1)
+        tc.metadata_schema = self.metadata_schema
+        tc.metadata = data
+        self.assertDictEqual(tc.metadata, data)
+
+    def test_bad_metadata(self):
+        metadata = self.metadata_example_data()
+        metadata["I really shouldn't be here"] = 6
+        tc = tskit.TableCollection(1)
+        tc.metadata_schema = self.metadata_schema
+        with self.assertRaises(exceptions.MetadataValidationError):
+            tc.metadata = metadata
+        self.assertEqual(tc.ll_tables.metadata, b"")
+
+
 class TestTableCollectionPickle(unittest.TestCase):
     """
     Tests that we can round-trip table collections through pickle.
diff --git a/python/tskit/tables.py b/python/tskit/tables.py
index e0bc3c36e9..f14a958b74 100644
--- a/python/tskit/tables.py
+++ b/python/tskit/tables.py
@@ -1884,6 +1884,30 @@ def sequence_length(self, sequence_length):
     def file_uuid(self):
         return self.ll_tables.file_uuid
 
+    @property
+    def metadata_schema(self) -> metadata.MetadataSchema:
+        """
+        The :class:`tskit.MetadataSchema` for this TableCollection.
+        """
+        return metadata.parse_metadata_schema(self.ll_tables.metadata_schema)
+
+    @metadata_schema.setter
+    def metadata_schema(self, schema: metadata.MetadataSchema) -> None:
+        # Check the schema is a valid schema instance by roundtripping it.
+        metadata.parse_metadata_schema(str(schema))
+        self.ll_tables.metadata_schema = str(schema)
+
+    @property
+    def metadata(self) -> Any:
+        """
+        The decoded metadata for this TableCollection.
+        """
+        return self.metadata_schema.decode_row(self.ll_tables.metadata)
+
+    @metadata.setter
+    def metadata(self, metadata: Any) -> None:
+        self.ll_tables.metadata = self.metadata_schema.validate_and_encode_row(metadata)
+
     def asdict(self):
         """
         Returns a dictionary representation of this TableCollection.
diff --git a/python/tskit/trees.py b/python/tskit/trees.py
index 6f6135e5b5..6bb3b62599 100644
--- a/python/tskit/trees.py
+++ b/python/tskit/trees.py
@@ -43,7 +43,7 @@
 import tskit.drawing as drawing
 import tskit.exceptions as exceptions
 import tskit.formats as formats
-import tskit.metadata as metadata
+import tskit.metadata as metadata_module
 import tskit.provenance as provenance
 import tskit.tables as tables
 import tskit.util as util
@@ -2829,19 +2829,21 @@ class _TableMetadataSchemas:
         Convenience class for returning schemas
         """
 
-        node: metadata.MetadataSchema
-        edge: metadata.MetadataSchema
-        site: metadata.MetadataSchema
-        mutation: metadata.MetadataSchema
-        migration: metadata.MetadataSchema
-        individual: metadata.MetadataSchema
-        population: metadata.MetadataSchema
+        node: metadata_module.MetadataSchema
+        edge: metadata_module.MetadataSchema
+        site: metadata_module.MetadataSchema
+        mutation: metadata_module.MetadataSchema
+        migration: metadata_module.MetadataSchema
+        individual: metadata_module.MetadataSchema
+        population: metadata_module.MetadataSchema
 
     def __init__(self, ll_tree_sequence):
         self._ll_tree_sequence = ll_tree_sequence
         metadata_schema_strings = self._ll_tree_sequence.get_table_metadata_schemas()
         metadata_schema_instances = {
-            name: metadata.parse_metadata_schema(getattr(metadata_schema_strings, name))
+            name: metadata_module.parse_metadata_schema(
+                getattr(metadata_schema_strings, name)
+            )
             for name in vars(self._TableMetadataSchemas)
             if not name.startswith("_")
         }
@@ -3155,6 +3157,22 @@ def sequence_length(self):
     def get_sequence_length(self):
         return self._ll_tree_sequence.get_sequence_length()
 
+    @property
+    def metadata(self) -> Any:
+        """
+        The decoded metadata for this TreeSequence.
+        """
+        return self.metadata_schema.decode_row(self._ll_tree_sequence.get_metadata())
+
+    @property
+    def metadata_schema(self) -> metadata_module.MetadataSchema:
+        """
+        The :class:`tskit.MetadataSchema` for this TreeSequence.
+        """
+        return metadata_module.parse_metadata_schema(
+            self._ll_tree_sequence.get_metadata_schema()
+        )
+
     @property
     def num_edges(self):
         """