diff --git a/src/wp-includes/blocks.php b/src/wp-includes/blocks.php
index f65ddb6c2e..e817286ff7 100644
--- a/src/wp-includes/blocks.php
+++ b/src/wp-includes/blocks.php
@@ -198,10 +198,38 @@ function parse_blocks( $content ) {
  * @return string Updated post content.
  */
 function do_blocks( $content ) {
+	// If there are blocks in this content, we shouldn't run wpautop() on it later.
+	$priority = has_filter( 'the_content', 'wpautop' );
+	if ( false !== $priority && doing_filter( 'the_content' ) && has_blocks( $content ) ) {
+		remove_filter( 'the_content', 'wpautop', $priority );
+		add_filter( 'the_content', '_restore_wpautop_hook', $priority + 1 );
+	}
+
 	$blocks = parse_blocks( $content );
 	return _recurse_do_blocks( $blocks, $blocks );
 }
 
+/**
+ * If do_blocks() needs to remove wp_autop() from the `the_content` filter, this re-adds it afterwards,
+ * for subsequent `the_content` usage.
+ *
+ * @access private
+ *
+ * @since 5.0.0
+ *
+ * @param string $content The post content running through this filter.
+ * @return string The unmodified content.
+ */
+function _restore_wpautop_hook( $content ) {
+	global $wp_filter;
+	$current_priority = $wp_filter['the_content']->current_priority();
+
+	add_filter( 'the_content', 'wpautop', $current_priority - 1 );
+	remove_filter( 'the_content', '_restore_wpautop_hook', $current_priority );
+
+	return $content;
+}
+
 /**
  * Helper function for do_blocks(), to recurse through the block tree.
  *
diff --git a/src/wp-includes/formatting.php b/src/wp-includes/formatting.php
index f408b1bfd0..5c974f9a06 100644
--- a/src/wp-includes/formatting.php
+++ b/src/wp-includes/formatting.php
@@ -458,11 +458,6 @@ function wpautop( $pee, $br = true ) {
 		return '';
 	}
 
-	// We don't need to autop posts with blocks in them.
-	if ( has_blocks( $pee ) ) {
-		return $pee;
-	}
-
 	// Just to make things a little easier, pad the end.
 	$pee = $pee . "\n";
 
diff --git a/tests/phpunit/tests/blocks/render.php b/tests/phpunit/tests/blocks/render.php
index a03397bc10..98e42249bc 100644
--- a/tests/phpunit/tests/blocks/render.php
+++ b/tests/phpunit/tests/blocks/render.php
@@ -75,13 +75,44 @@ class WP_Test_Block_Render extends WP_UnitTestCase {
 		// Block rendering add some extra blank lines, but we're not worried about them.
 		$block_filtered_content = preg_replace( "/\n{2,}/", "\n", $block_filtered_content );
 
-		$this->assertEquals( $classic_filtered_content, $block_filtered_content );
+		$this->assertEquals( trim( $classic_filtered_content ), trim( $block_filtered_content ) );
 	}
 
 	function handle_shortcode( $atts, $content ) {
 		return $content;
 	}
 
+	/**
+	 * @ticket 45290
+	 */
+	public function test_blocks_arent_autopeed() {
+		$expected_content = 'test';
+		$test_content     = "<!-- wp:fake/block -->\n$expected_content\n<!-- /wp:fake/block -->";
+
+		$current_priority = has_action( 'the_content', 'wpautop' );
+
+		$filtered_content = trim( apply_filters( 'the_content', $test_content ) );
+
+		$this->assertEquals( $expected_content, $filtered_content );
+
+		// Check that wpautop() is still defined in the same place.
+		$this->assertSame( $current_priority, has_action( 'the_content', 'wpautop' ) );
+		// ... and that the restore function has removed itself.
+		$this->assertFalse( has_action( 'the_content', '_restore_wpautop_hook' ) );
+
+		$test_content     = 'test';
+		$expected_content = "<p>$test_content</p>";
+
+		$current_priority = has_action( 'the_content', 'wpautop' );
+
+		$filtered_content = trim( apply_filters( 'the_content', $test_content ) );
+
+		$this->assertEquals( $expected_content, $filtered_content );
+
+		$this->assertSame( $current_priority, has_action( 'the_content', 'wpautop' ) );
+		$this->assertFalse( has_action( 'the_content', '_restore_wpautop_hook' ) );
+	}
+
 	/**
 	 * @ticket 45109
 	 */