diff -u b/core/modules/file/src/Entity/File.php b/core/modules/file/src/Entity/File.php
--- b/core/modules/file/src/Entity/File.php
+++ b/core/modules/file/src/Entity/File.php
@@ -7,6 +7,7 @@
 
 namespace Drupal\file\Entity;
 
+use Drupal\Component\Utility\Crypt;
 use Drupal\Core\Entity\ContentEntityBase;
 use Drupal\Core\Entity\EntityStorageInterface;
 use Drupal\Core\Entity\EntityTypeInterface;
@@ -194,7 +195,10 @@
   public function preSave(EntityStorageInterface $storage) {
     parent::preSave($storage);
 
-    $this->setSize(filesize($this->getFileUri()));
+    $uri = $this->getFileUri();
+    $this->setSize(filesize($uri));
+    // Save the hash of the URI so we can enforce uniqueness.
+    $this->get('uri_hash')->value = Crypt::hashBase64($uri);
   }
 
   /**
@@ -249,10 +253,17 @@
     $fields['uri'] = BaseFieldDefinition::create('uri')
       ->setLabel(t('URI'))
       ->setDescription(t('The URI to access the file (either local or remote).'))
-      ->setSetting('is_ascii', TRUE)
       ->setSetting('max_length', 255)
       ->setSetting('case_sensitive', TRUE);
 
+    $fields['uri_hash'] = BaseFieldDefinition::create('string')
+      ->setLabel(t('URI Hash'))
+      ->setDescription(t('The hashed URI. Saved to enforce uniqueness.'))
+      ->setSetting('is_ascii', TRUE)
+      // As this is a base64 encoded sha256 hash, 128 ought to be enough.
+      ->setSetting('max_length', 128)
+      ->setSetting('case_sensitive', TRUE);
+
     $fields['filemime'] = BaseFieldDefinition::create('string')
       ->setLabel(t('File MIME type'))
       ->setSetting('is_ascii', TRUE)
reverted:
--- b/core/modules/file/src/FileStorage.php
+++ a/core/modules/file/src/FileStorage.php
@@ -8,7 +8,6 @@
 namespace Drupal\file;
 
 use Drupal\Core\Entity\Sql\SqlContentEntityStorage;
-use Drupal\Core\Entity\EntityInterface;
 
 /**
  * File storage for files.
@@ -18,39 +17,6 @@
   /**
    * {@inheritdoc}
    */
-  protected function doLoadMultiple(array $ids = NULL) {
-    $entities = parent::doLoadMultiple($ids);
-    foreach ($entities as $entity) {
-      // @see FileStorage::doSave()
-      $entity->setFileUri($this->uriFromAscii($entity->getFileUri()));
-    }
-  }
-
-  /**
-   * {@inheritdoc}
-   */
-  public function loadByProperties(array $values = array()) {
-    foreach ($values as $name => $value) {
-      if ($name == 'uri') {
-        // @see FileStorage::doSave()
-        $values[$name] = $this->uriToAscii($value);
-      }
-    }
-    parent::loadByProperties($values);
-  }
-
-  /**
-   * {@inheritdoc}
-   */
-  public function doSave($id, EntityInterface $entity) {
-    $entity->setFileUri($this->uriToAscii($entity->getFileUri()));
-    parent::doSave($id, $entity);
-    $entity->setFileUri($this->uriFromAscii($entity->getFileUri()));
-  }
-
-  /**
-   * {@inheritdoc}
-   */
   public function spaceUsed($uid = NULL, $status = FILE_STATUS_PERMANENT) {
     $query = $this->database->select($this->entityType->getBaseTable(), 'f')
       ->condition('f.status', $status);
@@ -61,33 +27,4 @@
     return $query->execute()->fetchField();
   }
 
-  /**
-   * Turns a URI string into an ASCII encoded string.
-   *
-   * This will be used to save non-ASCII data into the URI field, which is
-   * marked as an ASCII field so it can contain a unique constraint and
-   * be 255 characters long at the same time.
-   *
-   * @param string $url
-   *   Provided URI, possibly non-ASCII.
-   *
-   * @return string
-   *   ASCII-encoded URI.
-   */
-  protected function uriToAscii($url) {
-    return str_replace('%3A', ':', str_replace('%2F', '/', rawurlencode($url)));
-  }
-
-  /**
-   * Inverse method of FileStorage::urlToAscii().
-   *
-   * @param string $url
-   *   ASCII encoded URI, from database.
-   *
-   * @return string
-   *   Originally provided URI.
-   */
-  protected function uriFromAscii($url) {
-    return rawurldecode($url);
-  }
 }
only in patch2:
unchanged:
--- a/core/modules/file/src/FileStorageSchema.php
+++ b/core/modules/file/src/FileStorageSchema.php
@@ -30,6 +30,9 @@ protected function getSharedTableFieldSchema(FieldStorageDefinitionInterface $st
           break;
 
         case 'uri':
+          $this->addSharedTableFieldIndex($storage_definition, $schema, TRUE);
+          break;
+        case 'uri_hash':
           $this->addSharedTableFieldUniqueKey($storage_definition, $schema, TRUE);
           break;
       }
only in patch2:
unchanged:
--- a/core/modules/file/src/Tests/SaveTest.php
+++ b/core/modules/file/src/Tests/SaveTest.php
@@ -8,6 +8,9 @@
 namespace Drupal\file\Tests;
 
 use Drupal\file\Entity\File;
+use Drupal\Core\Entity\EntityStorageException;
+use Drupal\Core\Entity\EntityStorageInterface;
+use Drupal\Core\Entity\Sql\SqlEntityStorageInterface;
 
 /**
  * File saving tests.
@@ -59,7 +62,7 @@ function testFileSave() {
 
     // Try to insert a second file with the same name apart from case insensitivity
     // to ensure the 'uri' index allows for filenames with different cases.
-    $uppercase_file = File::create(array(
+    $uppercase_values = array(
       'uid' => 1,
       'filename' => 'DRUPLICON.txt',
       'uri' => 'public://DRUPLICON.txt',
@@ -67,10 +70,25 @@ function testFileSave() {
       'created' => 1,
       'changed' => 1,
       'status' => FILE_STATUS_PERMANENT,
-    ));
+    );
+    $uppercase_file = File::create($uppercase_values);
     file_put_contents($uppercase_file->getFileUri(), 'hello world');
     $uppercase_file->save();
 
+    $storage = \Drupal::entityManager()->getStorage('file');
+    $this->assertTrue($storage instanceof EntityStorageInterface, 'Storage object implements EntityStorageInterface.');
+    if ($storage instanceof SqlEntityStorageInterface) {
+      // Ensure the database URL uniqueness constraint is triggered.
+      $uppercase_file_duplicate = File::create($uppercase_values);
+      file_put_contents($uppercase_file_duplicate->getFileUri(), 'hello world');
+      try {
+        $uppercase_file_duplicate->save();
+      } catch (EntityStorageException $e) {
+        $exception_triggered = (0 === strpos($e->getCode(), '23'));
+      }
+      $this->assertTrue($exception_triggered, 'SQL uniqueness constraint is triggered');
+    }
+
     // Ensure that file URI entity queries are case sensitive.
     $fids = \Drupal::entityQuery('file')
       ->condition('uri', $uppercase_file->getFileUri())
only in patch2:
unchanged:
--- a/core/modules/migrate_drupal/src/Tests/d6/MigrateFileTest.php
+++ b/core/modules/migrate_drupal/src/Tests/d6/MigrateFileTest.php
@@ -8,6 +8,7 @@
 namespace Drupal\migrate_drupal\Tests\d6;
 
 use Drupal\Component\Utility\Random;
+use Drupal\Component\Utility\Crypt;
 use Drupal\migrate\MigrateExecutable;
 use Drupal\migrate\Tests\MigrateDumpAlterInterface;
 use Drupal\migrate_drupal\Tests\d6\MigrateDrupal6TestBase;
@@ -63,6 +64,7 @@ public function testFiles() {
     $this->assertIdentical('Image1.png', $file->getFilename());
     $this->assertIdentical('39325', $file->getSize());
     $this->assertIdentical('public://image-1.png', $file->getFileUri());
+    $this->assertIdentical(Crypt::hashBase64('public://image-1.png'), $file->get('uri_hash')->value);
     $this->assertIdentical('image/png', $file->getMimeType());
     // It is pointless to run the second half from MigrateDrupal6Test.
     if (empty($this->standalone)) {