diff --git a/moto/ec2/models.py b/moto/ec2/models.py
index cb7ba0ff..89dd753f 100644
--- a/moto/ec2/models.py
+++ b/moto/ec2/models.py
@@ -3547,6 +3547,7 @@ class Route(object):
         self,
         route_table,
         destination_cidr_block,
+        destination_ipv6_cidr_block,
         local=False,
         gateway=None,
         instance=None,
@@ -3554,9 +3555,12 @@ class Route(object):
         interface=None,
         vpc_pcx=None,
     ):
-        self.id = generate_route_id(route_table.id, destination_cidr_block)
+        self.id = generate_route_id(
+            route_table.id, destination_cidr_block, destination_ipv6_cidr_block
+        )
         self.route_table = route_table
         self.destination_cidr_block = destination_cidr_block
+        self.destination_ipv6_cidr_block = destination_ipv6_cidr_block
         self.local = local
         self.gateway = gateway
         self.instance = instance
@@ -3632,6 +3636,7 @@ class RouteBackend(object):
         self,
         route_table_id,
         destination_cidr_block,
+        destination_ipv6_cidr_block=None,
         local=False,
         gateway_id=None,
         instance_id=None,
@@ -3656,9 +3661,10 @@ class RouteBackend(object):
                     gateway = self.get_internet_gateway(gateway_id)
 
             try:
-                ipaddress.IPv4Network(
-                    six.text_type(destination_cidr_block), strict=False
-                )
+                if destination_cidr_block:
+                    ipaddress.IPv4Network(
+                        six.text_type(destination_cidr_block), strict=False
+                    )
             except ValueError:
                 raise InvalidDestinationCIDRBlockParameterError(destination_cidr_block)
 
@@ -3668,6 +3674,7 @@ class RouteBackend(object):
         route = Route(
             route_table,
             destination_cidr_block,
+            destination_ipv6_cidr_block,
             local=local,
             gateway=gateway,
             instance=self.get_instance(instance_id) if instance_id else None,
diff --git a/moto/ec2/responses/route_tables.py b/moto/ec2/responses/route_tables.py
index b5d65f83..a91d0231 100644
--- a/moto/ec2/responses/route_tables.py
+++ b/moto/ec2/responses/route_tables.py
@@ -16,6 +16,7 @@ class RouteTables(BaseResponse):
     def create_route(self):
         route_table_id = self._get_param("RouteTableId")
         destination_cidr_block = self._get_param("DestinationCidrBlock")
+        destination_ipv6_cidr_block = self._get_param("DestinationIpv6CidrBlock")
         gateway_id = self._get_param("GatewayId")
         instance_id = self._get_param("InstanceId")
         nat_gateway_id = self._get_param("NatGatewayId")
@@ -25,6 +26,7 @@ class RouteTables(BaseResponse):
         self.ec2_backend.create_route(
             route_table_id,
             destination_cidr_block,
+            destination_ipv6_cidr_block,
             gateway_id=gateway_id,
             instance_id=instance_id,
             nat_gateway_id=nat_gateway_id,
diff --git a/moto/ec2/utils.py b/moto/ec2/utils.py
index c07c470a..b8c19b58 100644
--- a/moto/ec2/utils.py
+++ b/moto/ec2/utils.py
@@ -189,7 +189,9 @@ def random_ipv6_cidr():
     return "2400:6500:{}:{}::/56".format(random_resource_id(4), random_resource_id(4))
 
 
-def generate_route_id(route_table_id, cidr_block):
+def generate_route_id(route_table_id, cidr_block, ipv6_cidr_block=None):
+    if ipv6_cidr_block and not cidr_block:
+        cidr_block = ipv6_cidr_block
     return "%s~%s" % (route_table_id, cidr_block)
 
 
diff --git a/tests/test_ec2/test_route_tables.py b/tests/test_ec2/test_route_tables.py
index 61fb33f9..7bb4db69 100644
--- a/tests/test_ec2/test_route_tables.py
+++ b/tests/test_ec2/test_route_tables.py
@@ -582,6 +582,17 @@ def test_create_route_with_invalid_destination_cidr_block_parameter():
         )
     )
 
+    route_table.create_route(
+        DestinationIpv6CidrBlock="2001:db8::/125", GatewayId=internet_gateway.id
+    )
+    new_routes = [
+        route
+        for route in route_table.routes
+        if route.destination_cidr_block != vpc.cidr_block
+    ]
+    new_routes.should.have.length_of(1)
+    new_routes[0].route_table_id.shouldnt.be.equal(None)
+
 
 @mock_ec2
 def test_create_route_with_network_interface_id():