Yes with reflection. This works (based on this answer):

(Note: this is a workaround due to lack of support for custom fonts, so if you want to change this situation please do star to up-vote the android issue here). Note: Do not leave “me too” comments on that issue, everyone who has stared it gets an email when you do that. So just “star” it please.

import java.lang.reflect.Field;
import android.content.Context;
import android.graphics.Typeface;

public final class FontsOverride {

    public static void setDefaultFont(Context context,
            String staticTypefaceFieldName, String fontAssetName) {
        final Typeface regular = Typeface.createFromAsset(context.getAssets(),
                fontAssetName);
        replaceFont(staticTypefaceFieldName, regular);
    }

    protected static void replaceFont(String staticTypefaceFieldName,
            final Typeface newTypeface) {
        try {
            final Field staticField = Typeface.class
                    .getDeclaredField(staticTypefaceFieldName);
            staticField.setAccessible(true);
            staticField.set(null, newTypeface);
        } catch (NoSuchFieldException e) {
            e.printStackTrace();
        } catch (IllegalAccessException e) {
            e.printStackTrace();
        }
    }
}

You then need to overload the few default fonts, for example in an application class:

public final class Application extends android.app.Application {
    @Override
    public void onCreate() {
        super.onCreate();
        FontsOverride.setDefaultFont(this, "DEFAULT", "MyFontAsset.ttf");
        FontsOverride.setDefaultFont(this, "MONOSPACE", "MyFontAsset2.ttf");
        FontsOverride.setDefaultFont(this, "SERIF", "MyFontAsset3.ttf");
        FontsOverride.setDefaultFont(this, "SANS_SERIF", "MyFontAsset4.ttf");
    }
}

Or course if you are using the same font file, you can improve on this to load it just once.

However I tend to just override one, say "MONOSPACE", then set up a style to force that font typeface application wide:

<resources>
    <style name="AppBaseTheme" parent="android:Theme.Light">
    </style>

    <!-- Application theme. -->
    <style name="AppTheme" parent="AppBaseTheme">
        <item name="android:typeface">monospace</item>
    </style>
</resources>

API 21 Android 5.0

I’ve investigated the reports in the comments that it doesn’t work and it appears to be incompatible with the theme android:Theme.Material.Light.

If that theme is not important to you, use an older theme, e.g.:

<style name="AppTheme" parent="android:Theme.Holo.Light.DarkActionBar">
    <item name="android:typeface">monospace</item>
</style>