diff --git a/python/CHANGELOG.rst b/python/CHANGELOG.rst
index 3d09d0b1af..f2b6c6d12f 100644
--- a/python/CHANGELOG.rst
+++ b/python/CHANGELOG.rst
@@ -4,6 +4,9 @@
 
 **Changes**
 
+- Tables in a table collection can be replaced using the replace_with method
+  (:user:`hyanwong`, :issue:`1489` :pr:`2389`)
+
 - SVG drawing routines now return a special string object that is automatically
   rendered in a Jupyter notebook (:user:`hyanwong`, :pr:`2377`)
 
diff --git a/python/tests/test_tables.py b/python/tests/test_tables.py
index 025d280631..1f573b5b94 100644
--- a/python/tests/test_tables.py
+++ b/python/tests/test_tables.py
@@ -823,6 +823,11 @@ def test_bad_offsets(self):
                     t.append_columns(**input_data)
                 input_data[offset_col.name] = np.copy(original_offset)
 
+    def test_replace_with_wrong_class(self):
+        t = self.table_class()
+        with pytest.raises(TypeError, match="wrong type"):
+            t.replace_with(tskit.BaseTable(None, None))
+
 
 class MetadataTestsMixin:
     """
@@ -3834,6 +3839,12 @@ def test_dump_load_errors(self, ts_fixture):
                 with pytest.raises(TypeError):
                     func(bad_filename)
 
+    def test_set_table(self):
+        tc = tskit.TableCollection()
+        for name, table in tc.table_name_map.items():
+            with pytest.raises(AttributeError, match="replace_with"):
+                setattr(tc, name, table)
+
 
 class TestEqualityOptions:
     def test_equals_provenance(self):
@@ -4383,6 +4394,20 @@ def test_set_columns_not_implemented(self):
         with pytest.raises(NotImplementedError):
             t.set_columns()
 
+    def test_replace_with(self, ts_fixture):
+        # Although replace_with is a BaseTable method, it is simpler to test it
+        # on the subclasses directly, as some differ e.g. in having metadata schemas
+        original_tables = ts_fixture.dump_tables()
+        original_tables.nodes.metadata_schema = tskit.MetadataSchema.permissive_json()
+        new_tables = ts_fixture.dump_tables()
+        new_tables.clear(clear_provenance=True, clear_metadata_schemas=True)
+
+        # write all the data back in again
+        for name, table in new_tables.table_name_map.items():
+            new_table = getattr(original_tables, name)
+            table.replace_with(new_table)
+        new_tables.assert_equals(original_tables)
+
 
 class TestSubsetTables:
     """
diff --git a/python/tskit/tables.py b/python/tskit/tables.py
index 08bfba0e22..74de73cc89 100644
--- a/python/tskit/tables.py
+++ b/python/tskit/tables.py
@@ -589,6 +589,23 @@ def append(self, row):
             }
         )
 
+    def replace_with(self, other):
+        # Overwrite the contents of this table with a copy of the other table
+        params = {}
+        for column in self.column_names:
+            try:
+                params[column] = getattr(other, column)
+            except AttributeError:
+                raise TypeError(
+                    "Replacement table has wrong type: it lacks a {column} column"
+                )
+        try:
+            # Not all tables have a metadata_schema: if they do, encode it with repr
+            params["metadata_schema"] = repr(other.metadata_schema)
+        except AttributeError:
+            pass
+        self.set_columns(**params)
+
     def clear(self):
         """
         Deletes all rows in this table.
@@ -2869,6 +2886,10 @@ class TableCollection(metadata.MetadataProvider):
     method.
     """
 
+    set_err_text = (
+        "Cannot set tables in a table collection: use table.replace_with() instead."
+    )
+
     def __init__(self, sequence_length=0):
         self._ll_tables = _tskit.TableCollection(sequence_length)
         super().__init__(self._ll_tables)
@@ -2880,6 +2901,10 @@ def individuals(self) -> IndividualTable:
         """
         return IndividualTable(ll_table=self._ll_tables.individuals)
 
+    @individuals.setter
+    def individuals(self, value):
+        raise AttributeError(self.set_err_text)
+
     @property
     def nodes(self) -> NodeTable:
         """
@@ -2887,6 +2912,10 @@ def nodes(self) -> NodeTable:
         """
         return NodeTable(ll_table=self._ll_tables.nodes)
 
+    @nodes.setter
+    def nodes(self, value):
+        raise AttributeError(self.set_err_text)
+
     @property
     def edges(self) -> EdgeTable:
         """
@@ -2894,6 +2923,10 @@ def edges(self) -> EdgeTable:
         """
         return EdgeTable(ll_table=self._ll_tables.edges)
 
+    @edges.setter
+    def edges(self, value):
+        raise AttributeError(self.set_err_text)
+
     @property
     def migrations(self) -> MigrationTable:
         """
@@ -2901,6 +2934,10 @@ def migrations(self) -> MigrationTable:
         """
         return MigrationTable(ll_table=self._ll_tables.migrations)
 
+    @migrations.setter
+    def migrations(self, value):
+        raise AttributeError(self.set_err_text)
+
     @property
     def sites(self) -> SiteTable:
         """
@@ -2908,6 +2945,10 @@ def sites(self) -> SiteTable:
         """
         return SiteTable(ll_table=self._ll_tables.sites)
 
+    @sites.setter
+    def sites(self, value):
+        raise AttributeError(self.set_err_text)
+
     @property
     def mutations(self) -> MutationTable:
         """
@@ -2915,6 +2956,10 @@ def mutations(self) -> MutationTable:
         """
         return MutationTable(ll_table=self._ll_tables.mutations)
 
+    @mutations.setter
+    def mutations(self, value):
+        raise AttributeError(self.set_err_text)
+
     @property
     def populations(self) -> PopulationTable:
         """
@@ -2922,6 +2967,10 @@ def populations(self) -> PopulationTable:
         """
         return PopulationTable(ll_table=self._ll_tables.populations)
 
+    @populations.setter
+    def populations(self, value):
+        raise AttributeError(self.set_err_text)
+
     @property
     def provenances(self) -> ProvenanceTable:
         """
@@ -2929,6 +2978,10 @@ def provenances(self) -> ProvenanceTable:
         """
         return ProvenanceTable(ll_table=self._ll_tables.provenances)
 
+    @provenances.setter
+    def provenances(self, value):
+        raise AttributeError(self.set_err_text)
+
     @property
     def indexes(self) -> TableCollectionIndexes:
         """