diff --git a/changelog.d/6451.bugfix b/changelog.d/6451.bugfix
new file mode 100644
index 0000000000..23b67583ec
--- /dev/null
+++ b/changelog.d/6451.bugfix
@@ -0,0 +1 @@
+Fix uploading multiple cross signing signatures for the same user.
diff --git a/synapse/storage/data_stores/main/schema/delta/56/signing_keys.sql b/synapse/storage/data_stores/main/schema/delta/56/signing_keys.sql
index 27a96123e3..5c5fffcafb 100644
--- a/synapse/storage/data_stores/main/schema/delta/56/signing_keys.sql
+++ b/synapse/storage/data_stores/main/schema/delta/56/signing_keys.sql
@@ -40,7 +40,8 @@ CREATE TABLE IF NOT EXISTS e2e_cross_signing_signatures (
     signature TEXT NOT NULL
 );
 
-CREATE UNIQUE INDEX e2e_cross_signing_signatures_idx ON e2e_cross_signing_signatures(user_id, target_user_id, target_device_id);
+-- replaced by the index created in signing_keys_nonunique_signatures.sql
+-- CREATE UNIQUE INDEX e2e_cross_signing_signatures_idx ON e2e_cross_signing_signatures(user_id, target_user_id, target_device_id);
 
 -- stream of user signature updates
 CREATE TABLE IF NOT EXISTS user_signature_stream (
diff --git a/synapse/storage/data_stores/main/schema/delta/56/signing_keys_nonunique_signatures.sql b/synapse/storage/data_stores/main/schema/delta/56/signing_keys_nonunique_signatures.sql
new file mode 100644
index 0000000000..0aa90ebf0c
--- /dev/null
+++ b/synapse/storage/data_stores/main/schema/delta/56/signing_keys_nonunique_signatures.sql
@@ -0,0 +1,22 @@
+/* Copyright 2019 The Matrix.org Foundation C.I.C.
+ *
+ * Licensed under the Apache License, Version 2.0 (the "License");
+ * you may not use this file except in compliance with the License.
+ * You may obtain a copy of the License at
+ *
+ *    http://www.apache.org/licenses/LICENSE-2.0
+ *
+ * Unless required by applicable law or agreed to in writing, software
+ * distributed under the License is distributed on an "AS IS" BASIS,
+ * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+ * See the License for the specific language governing permissions and
+ * limitations under the License.
+ */
+
+/* The cross-signing signatures index should not be a unique index, because a
+ * user may upload multiple signatures for the same target user. The previous
+ * index was unique, so delete it if it's there and create a new non-unique
+ * index. */
+
+DROP INDEX IF EXISTS e2e_cross_signing_signatures_idx; CREATE INDEX IF NOT
+EXISTS e2e_cross_signing_signatures2_idx ON e2e_cross_signing_signatures(user_id, target_user_id, target_device_id);