WordPress “Loop” with large set of results

You can use the Transients API to cache the entire HTML output so the queries are not done every time the page is loaded:

$transient="my-300-posts";
$timeout   = 3600; // 1 hour

if ( false === $out = get_transient( $transient ) ) {

    $args = array( YOUR ARGS GO HERE );
    $posts = get_posts( $args );
    if ( $posts ) {
        foreach ( $posts as $post ) {
            $out .= get_the_title( $post->ID );
            $out .= // whatever else you want to output...
        }
    }

    if ( $out ) {
        set_transient( $transient, $out, $timeout );
    }

}

echo $out;

However, you’re still serving 300 post thumbnails on one page load, which is a lot of data to transfer.

(You also need to delete the transient on the save_post and delete_post hooks)

Maybe you’d be better off with infinite scrolling? It’s an option in the Jetpack plugin.