Create custom SQL for SQL Server. Yes, it had to be that ugly, but it works. Falling on my sword over here...

wagtail/wagtailimages/migrations/0004_make_focal_point_key_not_nullable.py

@@ -11,6 +11,19 @@ def remove_duplicate_renditions(apps, schema_editor):
                 SELECT CONCAT(image_id, '-', filter_id) FROM (SELECT * FROM `wagtailimages_rendition`) as x WHERE `focal_point_key` IS NULL GROUP BY image_id, filter_id HAVING COUNT(*) > 1
             ) AND `focal_point_key` IS NULL
         """)
+    elif schema_editor.connection.vendor == 'microsoft':
+        schema_editor.execute("""
+            DELETE FROM [wagtailimages_rendition] WHERE CAST(image_id AS VARCHAR(MAX)) + '-' + CAST(filter_id AS VARCHAR(MAX)) IN (
+                SELECT CAST(image_id AS VARCHAR(MAX)) + '-' + CAST(filter_id AS VARCHAR(MAX)) FROM [wagtailimages_rendition] WHERE focal_point_key IS NULL GROUP BY image_id, filter_id HAVING COUNT(*) > 1
+            ) AND focal_point_key IS NULL
+        """)
+        schema_editor.execute("""
+            DECLARE @constraint_name VARCHAR(MAX)
+            SELECT @constraint_name = CONSTRAINT_NAME FROM INFORMATION_SCHEMA.TABLE_CONSTRAINTS WHERE TABLE_NAME='wagtailimages_rendition' AND CONSTRAINT_TYPE='UNIQUE'
+            EXEC('ALTER TABLE [wagtailimages_rendition] DROP CONSTRAINT ' + @constraint_name)
+            ALTER TABLE [wagtailimages_rendition] ALTER COLUMN [focal_point_key] NVARCHAR(255) NOT NULL
+            EXEC('ALTER TABLE [wagtailimages_rendition] ADD CONSTRAINT ' + @constraint_name + ' UNIQUE NONCLUSTERED (image_id, filter_id, focal_point_key)')
+        """)
     else:
         schema_editor.execute("""
             DELETE FROM wagtailimages_rendition WHERE image_id || '-' || filter_id IN (
@@ -26,6 +39,7 @@ class Migration(migrations.Migration):
 
     operations = [
         migrations.RunPython(remove_duplicate_renditions),
+
         migrations.AlterField(
             model_name='rendition',
             name='focal_point_key',