diff --git a/moto/ec2/models.py b/moto/ec2/models.py
index f8ebd02ec..cb7ba0ff2 100644
--- a/moto/ec2/models.py
+++ b/moto/ec2/models.py
@@ -3639,26 +3639,31 @@ class RouteBackend(object):
         interface_id=None,
         vpc_peering_connection_id=None,
     ):
+        gateway = None
+        nat_gateway = None
+
         route_table = self.get_route_table(route_table_id)
 
         if interface_id:
-            self.raise_not_implemented_error("CreateRoute to NetworkInterfaceId")
+            # for validating interface Id whether it is valid or not.
+            self.get_network_interface(interface_id)
 
-        gateway = None
-        if gateway_id:
-            if EC2_RESOURCE_TO_PREFIX["vpn-gateway"] in gateway_id:
-                gateway = self.get_vpn_gateway(gateway_id)
-            elif EC2_RESOURCE_TO_PREFIX["internet-gateway"] in gateway_id:
-                gateway = self.get_internet_gateway(gateway_id)
+        else:
+            if gateway_id:
+                if EC2_RESOURCE_TO_PREFIX["vpn-gateway"] in gateway_id:
+                    gateway = self.get_vpn_gateway(gateway_id)
+                elif EC2_RESOURCE_TO_PREFIX["internet-gateway"] in gateway_id:
+                    gateway = self.get_internet_gateway(gateway_id)
 
-        try:
-            ipaddress.IPv4Network(six.text_type(destination_cidr_block), strict=False)
-        except ValueError:
-            raise InvalidDestinationCIDRBlockParameterError(destination_cidr_block)
+            try:
+                ipaddress.IPv4Network(
+                    six.text_type(destination_cidr_block), strict=False
+                )
+            except ValueError:
+                raise InvalidDestinationCIDRBlockParameterError(destination_cidr_block)
 
-        nat_gateway = None
-        if nat_gateway_id is not None:
-            nat_gateway = self.nat_gateways.get(nat_gateway_id)
+            if nat_gateway_id is not None:
+                nat_gateway = self.nat_gateways.get(nat_gateway_id)
 
         route = Route(
             route_table,
diff --git a/tests/test_ec2/test_route_tables.py b/tests/test_ec2/test_route_tables.py
index a64fbae1a..61fb33f90 100644
--- a/tests/test_ec2/test_route_tables.py
+++ b/tests/test_ec2/test_route_tables.py
@@ -462,7 +462,7 @@ def test_routes_not_supported():
     # Create
     conn.create_route.when.called_with(
         main_route_table.id, ROUTE_CIDR, interface_id="eni-1234abcd"
-    ).should.throw(NotImplementedError)
+    ).should.throw("InvalidNetworkInterfaceID.NotFound")
 
     # Replace
     igw = conn.create_internet_gateway()
@@ -583,6 +583,32 @@ def test_create_route_with_invalid_destination_cidr_block_parameter():
     )
 
 
+@mock_ec2
+def test_create_route_with_network_interface_id():
+    ec2 = boto3.resource("ec2", region_name="us-west-2")
+    ec2_client = boto3.client("ec2", region_name="us-west-2")
+
+    vpc = ec2.create_vpc(CidrBlock="10.0.0.0/16")
+    subnet = ec2.create_subnet(
+        VpcId=vpc.id, CidrBlock="10.0.0.0/24", AvailabilityZone="us-west-2a"
+    )
+
+    route_table = ec2_client.create_route_table(VpcId=vpc.id)
+
+    route_table_id = route_table["RouteTable"]["RouteTableId"]
+
+    eni1 = ec2_client.create_network_interface(
+        SubnetId=subnet.id, PrivateIpAddress="10.0.10.5"
+    )
+
+    route = ec2_client.create_route(
+        NetworkInterfaceId=eni1["NetworkInterface"]["NetworkInterfaceId"],
+        RouteTableId=route_table_id,
+    )
+
+    route["ResponseMetadata"]["HTTPStatusCode"].should.equal(200)
+
+
 @mock_ec2
 def test_describe_route_tables_with_nat_gateway():
     ec2 = boto3.client("ec2", region_name="us-west-1")